Raj hooks up with a recently separated woman, Nell, after one of his lectures at the planetarium. Her husband, Oliver, confronts Raj at the planetarium and then breaks down over the end of his marriage. After comforting Oliver, Raj talks to Nell and convinces her to give her husband another chance. Meanwhile, after diving once again into string theory and sprawling his work across his and Amy's apartment, Sheldon approaches a reluctant Leonard and Penny and convinces them to let him use his old room to study for a three-day trial period with an agreement to be quiet and stay out of their way. Sheldon surprisingly sticks to this agreement, being a reasonably good guest, which shockingly frustrates Leonard to no end. After Leonard lets out his frustrations, Sheldon then renegotiates the guest tenancy agreement for an extra few days and resumes being his normal demanding self, much to Leonard's relief.
Penny runs into her ex-boyfriend Zack, who has gotten rich from selling his company and married a similarly dim-witted woman named Marissa. Meeting with Leonard and Penny, they say Zack is infertile and ask to pay Leonard as a sperm donor so they can have a baby. Leonard is flattered, but Penny finds it creepy. Leonard says that since Penny decided she did not want to have children, he should be allowed to help another couple with this issue. Sheldon advises him to think about the emotional toll this could have on him. Leonard says he will not do it if Penny objects; Penny says she will support whatever decision Leonard makes. Meanwhile, Raj tries to get Anu back but she points out he just wanted to be married like his friends. Raj points out that Anu is similarly looking for a quick marriage. He admits to Anu that he really likes her and they decide to start their relationship as just dating.
Bert asks for Sheldon's help in a geology research project relating to dark matter. Sheldon secretly agrees, but is too embarrassed to admit he is working with rocks. Bert finds out about this and ends their partnership. After talking with Amy, Sheldon goes to apologize, only to find Leonard has taken his place. Meanwhile, Raj runs into Ruchi again and goes out with her, but she does not believe in romantic love. After Howard and Bernadette tell Raj that he can just have sex with Ruchi, he agrees to keep it casual.
The show originally centered on five characters living in Pasadena, California: Leonard Hofstadter and Sheldon Cooper, both physicists at Caltech, who share an apartment; Penny, a waitress and aspiring actress who lives across the hall; and Leonard and Sheldon's similarly geeky and socially awkward friends and co-workers, aerospace engineer Howard Wolowitz and astrophysicist Raj Koothrappali. Over time, supporting characters were promoted to starring roles, including neuroscientist Amy Farrah Fowler, microbiologist Bernadette Rostenkowski, physicist Leslie Winkle and comic book store owner Stuart Bloom.
Getting called into Human Resources for Amy's outburst, Mrs. Davis tells her and Sheldon they are blowing their chances at the Nobel Prize. Amy would be the fourth woman to win in Physics, pressuring her to be a role model for women everywhere. To calm down, they try a sensory deprivation tank, which Sheldon loves, but Amy's mood only worsens. Sheldon does not know how to help and ends up holding her while singing "Soft Kitty". A newly confident Amy goes back to Human Resources to be allowed to campaign again and shares a drink with Mrs. Davis. Meanwhile, Howard buys a scooter to ride with Raj like in the old days. Bernadette finds out and makes him sell it since it's too dangerous. Bert buys it and ends up meeting a nurse after he dislocates his arm in a wreck.
Sheldon's mother Mary refuses to attend his wedding unless he invites his older brother George, with whom he is no longer speaking. Sheldon and Leonard fly to Texas to talk to George, who now owns a chain of tire stores. He refuses to attend and later explains to Leonard and Sheldon that the family sacrificed a lot to fund Sheldon's education, and he was stuck caring for their mother and sister Missy after their father died while Sheldon was in college. Sheldon never thanked him for this. Leonard takes George back to the hotel room where Sheldon apologizes for what he did and the brothers reconcile. George agrees to attend the wedding. Meanwhile, Howard and Bernadette's children contract pinkeye, infecting everyone except Penny, much to Amy's fury.
After Sheldon reminds the guys about the time they mined Bitcoin without him, the guys go on a quest to find their suddenly valuable missing cryptocurrency. They realize the currency is on a laptop which Leonard gave to Penny when they dating, which she then gave to her ex-boyfriend Zack. After Leonard and Penny go to Zack's apartment, he shows them a seven-year-old video that Penny recorded on the laptop soon after she broke up with Leonard. Leonard is touched by the video which shows a drunk Penny lamenting the break-up of her relationship with him.