Benton commits perjury on the witness stand in order to gain custody of Reese. When Romano refuses to give him a more even schedule, Peter resigns and seeks a job at the clinic where Cleo is newly employed. Benton is granted custody of Reese and he and Cleo decide to move to the suburbs together. Meanwhile, Carter's father visits for Christmas with the news that he's getting divorced, Weaver and Sandy Lopez finally go on a date, and Abby catches Nicole in the maternity ward, recovering from an abortion.

Drs. Corday and Greene are awkward when working together in the ER. Dr. Weaver treats victims of an intense fire that may take the life of a dear friend.

Just when the ER is understaffed and swamped, two children who were brought in turn out to have full blown smallpox. The entire ER must be locked down. The staff needs to improvise while they battle not only the disease but also frayed tempers.

Dr. Carter, Abby and other staff of the ER are quarantined as the CDC investigate a mysterious, deadly outbreak.