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- Actor-Inspired Element: Goran Visnjic came up with the name for his character, Luka Kovac after the writers were unable to come up with an appropriate Croatian name. The character is named for Goran Visnjic's nephew, Luka and his best friend, Kovac.
- Disabled Character, Disabled Actor: Matthew Watkins (who played Dr. Peter Benton's deaf son, Reese) is deaf in real life.
- Real-Life Relative:
- George Clooney's cousin, actor Miguel Ferrer and aunt, actress & singer Rosemary Clooney each made guest appearances on the show.
- David Brisbin (who played anesthelogist Alexander Babcock) is Laura Innes' husband
- What Could Have Been
- In the pilot episode, Carol Hathaway (Julianna Margulies) was supposed to have died from her suicide attempt, but the character tested so well with audiences, Margulies was kept on the show and Carol ended up surviving.
- "ER" was originally planned to be released as a film (which Steven Spielberg was supposed to direct), but the plans fell through and the project eventually became a TV series.
- Glenne Headley (Dr. Abby Keaton) was pregnant when she signed on to do her story arc in the third season. Originally, the writers floated the idea of writing Headley's pregnancy into the show, but decided against it because they thought audiences would have difficulty accepting Dr. John Carter (Noah Wyle) having a relationship with a pregnant woman.
- Erin Harkins (Leslie Bibb) was supposed to have died in the season 9 episode, "Hindsight" where she & Luka Kovac were in a car accident, but the producers changed their mind after the episode had been written and it ended on an ambigious ending on if Harkins survived the accident; a few episodes later, she resurfaced alive & well.
- Michael Beach was originally suggested for the role of Dr. Peter Benton, but John Wells felt that he didn't complete the ensemble & Eriq La Salle was later cast in the role instead. Beach would later appear on the series as Jeanie Boulet's ex-husband, Al.
- Lisa Zane originally auditioned for the part of Dr. Susan Lewis (in which Sherry Stringfield was cast in the role), but she would later play a love interest for Doug Ross.
- George Clooney's character was originally going to named Tom Ross & Julianna Margulies' character was originally going to be named Barb Hathaway.