During the season, actress Kaley Cuoco was absent from two episodes after she fell off a horse and the horse accidentally crushed her leg.
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Penny suggests that he should first go out with Amy on a date.
Melissa Rauch and Mayim Bialik were upgraded to the main cast during the fourth season as Dr. Jim Parsons won the Primetime Emmy Award for Outstanding Lead Actor in a Comedy Series at the 63rd Primetime Emmy Awards for the episode "The Agreement Dissection".
Penny dates a couple of guys including the dense Zack who likes the "science dudes", Sheldon begins a platonic relationship with Amy, Howard reconnects with Bernadette eventually asking her to marry him, Leonard begins to date Raj's sister Priya, Penny becomes friends with Amy and expresses regret at breaking up with Leonard.
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Later Howard calls Leonard, saying it "happened again", indicating that he again tried to use the arm to masturbate and got his genitals stuck for the second time.
Meanwhile, Penny comes to know of Sheldon's new friend Amy and is shocked when Sheldon announces his plans to conceive a child with her via in-vitro fertilization based on their superior genetics using Penny as a surrogate.
Later at home, he uses the arm as a massager and even tries to use it to masturbate, but executes the wrong program and gets his genitals stuck to the arm, forcing him to call Leonard and Raj for help.
They take him to the hospital (along with the arm and Howard's laptop containing the program for the arm movement) where the nurse turns off the laptop, which releases the arm's grip on Howard's genitals.
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Season four starts four months after the end of season 3. Johnny Galecki submitted the episode "The Benefactor Factor" for consideration due to his nomination for the Primetime Emmy Award for Outstanding Lead Actor in a Comedy Series at the 63rd Primetime Emmy Awards.