Grissom is confronted with new evidence while on the stand of a murder trial of a restaurant owner. This development requires the reopening of the case and Eckley initiates an inquiry into Grissom and his team. The results of the inquiry lead to dramatic changes of the CSI team and the series.

A serial killer strikes again, and the CSI team tries new technology using evidence from a prior killing. They find a fingerprint belonging to Jesse Acheson, who becomes the prime suspect. A boy confesses to the killing of his brother, but evidence suggests that he may not have committed the crime.

Two amorous freshmen are found dead on a sleeping bag in a dorm room, and Sara and Greg run into one dead end after another as they try to determine why the students were killed. Warrick, Nick and Catherine figure out how a man is found dead in the center of a crop circle. Ecklie is called into duty for a man found dead in his car and his body later goes missing.