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Leslie Winkle, Ph.D., is an experimental physicist at the California Institute of Technology who works in the same lab as Leonard. She is essentially his female counterpart, equipped with the same black framed glasses and zippered hoodies. Whenever depicted in the lab, she is always using the equipment inappropriately to prepare food, such as flash-freezing a banana with liquid nitrogen and then shattering it with a hammer to put in her cereal, or using a helium-neon laser to heat a cup of instant soup. She dates Leonard on-and-off, and later Howard. Because of her shallow and manipulative nature, she is arguably the central antagonist of the second series. Leslie made her final appearance in "The Lunar Excitation" and left the series after that.
Leslie specializes in high energy physics, particularly searching for supersymmetry with like-sign dileptons. Leslie believes loop quantum gravity is the future of physics and better unites quantum mechanics with general relativity than string theory does. She posits that only loop quantum gravity calculates the entropy of black holes and expects quantized spacetime to manifest itself as minute differences in the speed of light for different colors.
Leslie takes her job seriously (when she isn't using the equipment for food reasons) and is very intelligent; she figured out a problem Sheldon had been working on without difficulty, much to his irritation. She cares so much about science that it affects her love life: her partner has to have the same scientific beliefs as her in order for them to stay together.
She is displayed as arrogant, condescending, and manipulative. When she and Howard started a "friends with benefits" relationship, she would only give him favors so long as he did as she wanted, admitting she could only be happy if she were in control. It is implied by dialogue (and said outright by Sheldon) that Leslie is promiscuous, as she suggested she tended to have orgies and mainly craved sex instead of a relationship.
Leslie makes her debut in "The Fuzzy Boots Corollary." Leonard, feeling his pursuit of his neighbor Penny is pointless, asked her out on a date because he thought she was in his league. She kisses him to see whether they have any chemistry, and turns the offer down when she feels no arousal. This, and his hopeless infatuation with Penny, causes Leonard to go into a state of depression. In her next appearance, she goes to Leonard's apartment to practice with her string quartet. She offers herself to Leonard to have sex, despite her previous rejection. She also inadvertently starts her rivalry with Sheldon when she solves a problem he was having and insults his intelligence. Assuming he and Leslie are now dating, Leonard goes to her only to find she just used him to satisfy her sex drive.
When the guys compete in a physics bowl and kick Sheldon off the team for his showboating behavior, Howard and Raj want Leslie to join. Leonard is understandably uneasy since she had used him, but agrees. Leslie at first rejects, but reconsiders when she discovers Sheldon has formed an opposing team. They win the bowl when Sheldon does not allow one of his partners to answer a question, which turned out to be right.
After Leonard and Penny decide not to pursue a relationship, Leslie approaches Leonard for a true relationship, despite her previous unwillingness. She allows him to have the "male role," and goes a bit far when she questions Leonard on any faults and genetic defects he has, and talks about having children on the first date. Sheldon is furious to discover this, but decides to consent after a talk with Penny. He and Leslie get into a fight over their scientific beliefs: Leslie prefers loop quantum gravity, while Sheldon prefers string theory. She expects Leonard to back her up, but when he sides with string, she dumps him, feeling they are not compatible. ("How will we raise the children?")
In the next episode she suggests Penny's recent addiction to an online game is due to a lack of a sex life. Sheldon agrees, as Penny had already admitted to having not had sex for a while, making it a rare]occasion that he agrees with Leslie on anything. In "The Cooper-Nowitzki Theorem," she makes fun of Sheldon after he gives an insulting lecture, but is derailed and disgusted when a graduate student named Ramona Nowitzki shows admiration for Sheldon. She even insults Leslie for Sheldon at one point (Sheldon is horrible at making snarky comebacks). Annoyed, she leaves.
"The Cushion Saturation" sees Leslie beginning a friends-with-benefits relationship with Howard when they are trapped in a shack during a paintball game. She gives him funds for his work and invites him on a trip to the CERN Large Hadron Collider project in Geneva. However, this turns out to be just Leslie's way to control Howard. Although initially reluctant to be in this sort of relationship, Howard later happily accepts his role as a "sex toy/arm candy." While Leslie does not physically appear in "The Vegas Renormalization," she plays a major part in the storyline when she calls off her "friends with benefits" relationship with Howard. Having developed genuine feelings for her, he becomes depressed and goes to Vegas with Leonard and Raj, where he sleeps with a prostitute to get over her.
Leslie is completely absent throughout season 3, only appearing in the finale, "The Lunar Excitation." Leonard shows up at her door and suggests they start their casual sex relationship again, and she responds "Let me think about that," before slamming the door in his face, and he realizes she is not coming back.
Leonard tries to ask her out because he considers her to be in his league and they decide to kiss to see if they have chemistry. Though Leslie compliments Leonard on his kissing technique, Leslie feels no arousal, and thus, no date occurs. She eventually puts forth an offer of sexual availability towards Leonard one evening after a string quartet practice in which she plays the violin, and the two engage in sexual intercourse, but she reveals that she only desires sex infrequently while distracted by a difficult project and subsequently dumps him, claiming she'll be satisfied until at least New Year's Eve.
Initially uncomfortable with commitment, she later comes to the realization that "there’s just a time in every woman’s life when she gets tired of waking up on a strange futon with a bunch of people she doesn’t know." Leslie briefly tries to rekindle her relationship with Leonard after his failed attempt at dating Penny, stating that she is "fully committed to the traditional relationship paradigm" and "who better to slow things down with than you?" She even considers Leonard as a potential mate, going so far as asking Leonard how many children they should have. However, it does not work out because of Leslie's belief in loop quantum gravity and Leonard's belief in string theory, which is, as she put it, a "deal-breaker." Leonard later said he did not care about their relationship. In "The Lunar Excitation", when Leonard appears at her door, Leslie reveals it has been eighteen months since they have seen each other. He asks if she wants to have sex with him just for fun like they used to. She quickly deduces that Penny dumped him and says she would like to think about it, before she slams the door. Leonard realizes she is not going to come back.
Sheldon originally had no animosity towards Leslie, as he was the one who encouraged Leonard to pursue her. When she insulted his intelligence, he came to hate her, considering her his "archenemy." Leslie displayed indifference to him, frequently calling him "dumb-ass" and insulting him at every opportunity. When she and Leonard began officially dating, Sheldon was furious, but decided to give his blessing. They then got into a fight over their scientific beliefs, and she broke up with Leonard when she discovered he shared Sheldon's belief. Interestingly, during "The Cushion Saturation," neither displayed any animosity towards each other, suggesting they have gotten past it.
In "The Cushion Saturation", during a Caltech paintball game, she begins an affair with Howard Wolowitz, making her the fifth woman to sleep with Howard without being paid. She allows him access to experimental equipment (like a rapid prototyper) in spite of budget cuts and a research trip to Geneva to check out CERN's supercollider, using some unrestricted grant money Caltech gave her. She essentially controls Howard with new equipment and research trips, so as to avoid a real relationship with feelings, and institutes a "friends with benefits" arrangement instead, which she is more used to. However, in "The Vegas Renormalization", she dumps him over the phone, simply saying "Howard, momma’s a rolling stone."
- Leslie seems to be the only person aside from Dennis Kim and Amy Farrah Fowler who has equal or greater intelligence than Sheldon.
- Sheldon became angry when Leslie and Leonard briefly dated, when, ironically, he was the one who suggested Leonard pursue her in the first place. When he did, however, he had no ill feelings towards her.
- He showed no anger when she and Howard were together, possibly because they were not officially dating. Also, since Leonard is his best friend, he probably didn't mind what Howard did.
- Leslie's only appearance in the third season was its finale, which was also her last appearance in the series.
- Out of all of Penny's rivals for Leonard's affection, Leslie was perhaps the smallest threat, as she and Leonard only dated for one episode.
- It has not been made clear what became of Leslie after season 3.