The emergency room of Chicago's County General, a teaching hospital, is on alert when a number of victims are rushed there for treatment after a building collapses nearby. The young residents and interns all help with the injured and deal with other patients and personal problems as well.

Dr. Susan Lewis (SHERRY STRINGFIELD) must console a fragile cancer patient. After being extremely drunk on his day off from work, charming pediatrician Dr. Douglas Ross (GEORGE CLOONEY) resumes his duties and confronts a mother whom he suspects of abusing her baby. Due to a shortage of staff on duty, Dr. Peter Benton (ERIQ LA SALLE), an intense and confident second-year surgical resident, must perform a major operation for which he may not be prepared. However, he manages to save the patient's life. Inexperienced medical student John Carter (NOAH WYLE), not yet a doctor, is forced to deal with several medical emergencies on his very first day in the emergency room.

In the midst of the chaos, Dr. Mark Greene (ANTHONY EDWARDS), the married chief resident, receives a lucrative job offer from a prestigious private practice. He is forced to make a choice between staying in this city hospital among colleagues and friends or listening to his wife who wants him to take the new job so he can be with his family more often. Although his commitment is with the emergency room, he worries about the effect this decision will have on his family.

Meanwhile, Ross' attraction to Nurse Carol Hathaway (JULIANNA MARGULIES) becomes apparent. Although they used to date, the relationship didn't work, and Hathaway is now dating a football player-turned-doctor. Several hours after she goes off duty, Hathaway is rushed back to the hospital--this time on a stretcher. Her new roommate found her unconscious. It appears that she is in critical condition due to a drug overdose. No one knows why she would attempt suicide.