Cosmologist Stephen Hawking made a short guest appearance in the fifth-season episode; in the eighth season, Hawking video conferences with Sheldon and Leonard, and makes another appearance in the 200th episode. In the fifth and sixth seasons, NASA astronaut Michael J. Massimino played himself multiple times in the role of Howard's fellow astronaut. Bill Nye appeared in the seventh and twelfth seasons.
"The Skank Reflex Analysis" "The Infestation Hypothesis" "The Wiggly Finger Catalyst" "The Russian Rocket Reaction" "The Rhinitis Revelation" "The Good Guy Fluctuation" "The Isolation Permutation" "The Flaming Spittoon Acquisition" "The Shiny Trinket Maneuver" "The Recombination Hypothesis" "The Beta Test Initiation" "The Werewolf Transformation" "The Hawking Excitation" "The Stag Convergence" "The Countdown Reflection"
The show's pilot episode premiered on September 24, 2007. This was the second pilot produced for the show. A different pilot was produced for the 2006–07 television season but never aired. The structure of the original unaired pilot was substantially different from the series' current form. The only main characters retained in both pilots were Leonard (Johnny Galecki) and Sheldon (Jim Parsons), who are named after Sheldon Leonard, a longtime figure in episodic television as producer, director and actor. A minor character, Althea (Vernee Watson), appeared in the first scene of both pilots that was retained generally as-is. The first pilot included two female lead characters - Katie, "a street-hardened, tough-as-nails woman with a vulnerable interior" (played by Canadian actress Amanda Walsh) and Gilda, a scientist colleague and friend of the male characters (played by Iris Bahr). Sheldon and Leonard meet Katie after she breaks up with a boyfriend and they invite her to share their apartment. Gilda is threatened by Katie's presence. Test audiences reacted negatively to Katie, but they liked Sheldon and Leonard. The original pilot used Thomas Dolby's hit "She Blinded Me with Science" as its theme song.
Howard dresses as Sheldon for Halloween at work, hurting Sheldon's feelings. When Howard does not apologize, Amy and Sheldon dress as Bernadette and Howard at Penny and Leonard's party, angering Bernadette. Sheldon and Bernadette later bond over their painful childhood memories. Leonard is upset that Penny does not seem to remember that their first kiss was on Halloween. Penny later admits she does remember, but does not like to think of their first kiss as an unromantic drunken hookup. She likes to imagine their first kiss was one they shared on Leonard's birthday, which pleases him.
When Leonard receives a braggy Christmas letter from his brother, he feels bad about how little he and Penny have achieved in the past year. Leonard wonders if he and Penny should be thinking about the next step after two years of marriage, like buying a house or having a baby. Penny tells him she wants to do all those things someday, but she has a bunch of stuff she would like to do first.