Eddie Kasalivich (Keanu Reeves) is a student machinist working with a team from the University of Chicago to obtain clean energy from water by efficiently splitting the hydrogen and oxygen molecules. While working at home, Eddie inadvertently discovers the secret. The machine is perfected the next day in the lab and everything appears to be working and stable. To celebrate, a party is thrown in the lab. That night after the party, project physicist Dr. Lily Sinclair (Rachel Weisz) tries to leave the lab but her car battery is dead. Eddie offers to take her home by taxi; but, later says they took a bus. Back in the lab, Drs. Alistair Barkley and Lu Chen are on their computers preparing to upload their discovery to the Internet so the world can share in this new discovery, speaking Chinese. Meanwhile, a van is seen driving toward the lab. Chen hears a noise and goes to investigate, but is kidnapped by unknown assailants as Alistair also comes under attack.
Meanwhile, Lily and Eddie arrive at her house and after making sure she is okay, Eddie heads back to the lab to get his motorcycle. As he arrives at the lab, he sees a van leaving and hears alarms coming from the lab. He runs inside to find Alistair with a plastic bag over his head and Chen nowhere to be found. The hydrogen reactor is dangerously unstable and Eddie is unable to shut it down. Realizing the reactor is going to overload, he speeds away on his bike as a concealed detonator triggers a massive hydrogen explosion that destroys the lab and surrounding streets. As rescue crews arrive, Eddie is questioned by the police and later the FBI about what happened the night of the blast. Upon returning with Lily to their homes, they realize that they are being framed as fake evidence is planted in both of their houses.
Both go on the run and head to an observatory belonging to Maggie McDermott, an old friend of Eddie's. After resting up, they contact Paul Shannon (Morgan Freeman), the man funding the project (along with DARPA), but they're almost caught in the process and barely manage to escape. As Eddie and Lily are evading more police, Paul meets with Lyman Earl Collier (Brian Cox) at C-Systems Research complex to discuss the current events. It becomes apparent that the plot to destroy the lab and frame Eddie and Lily for it was orchestrated by the company, and that Lyman is responsible. Despite some disagreement, Paul and Lyman decide to continue the hunt for Eddie and Lily, a task made easier when Eddie sends a coded message to Paul requesting another place to meet. At this new rendezvous, Paul reveals he was involved, but wants to talk somewhere else. The meeting ends in an ambush, and Lily is captured as Eddie barely escapes.
- Keanu Reeves as Eddie Kasalivich
- Morgan Freeman as Dr. Paul Shannon
- Rachel Weisz as Dr. Lily Sinclair
- Fred Ward as FBI Agent Leon Ford
- Kevin Dunn as FBI Agent Doyle
- Brian Cox as Lyman Earl Collier
- Joanna Cassidy as Maggie McDermott
- Nicholas Rudall as Dr. Alistair Barkley
- Tzi Ma as Dr. Lu Chen
Large portions of the film were shot on location in and around Chicago, Illinois, including the University of Chicago, Argonne National Laboratory, the Museum of Science and Industry, the Field Museum of Natural History, Michigan Avenue,and the James R. Thompson Center (Atrium Mall). Additional scenes were shot at Yerkes Observatory in Williams Bay, Wisconsin, on Geneva Lake in southern Wisconsin, interiors of the U.S. Capitol were shot at the Wisconsin State Capitol, in Madison, Wisconsin and at Inland Steel (now known as MITTAL Steel) in East Chicago, Indiana. Because of the cold Great Lakes winter and filming taking place during record breaking winter weather besides, unique challenges were present for the cast and crew. Morgan Freeman noted that "It was difficult for everyone, particularly for me because I'm tropical," he said. "I don't do cold weather. This is Chicago...in the winter. I was actually ill and in bed four days at a crack. It was really rough." Among the extras in the film were U.S. Rep. (and current U.S. Senator) Tammy Baldwin (D-Wis.) 
"Chain Reaction" debuted at #8 at the box office, grossing $7,546,000 during its opening weekend.
Domestically, the film made $19,993,201, $14,919,074 in the foreign market and $36,400,000 worldwide.
On Rotten Tomatoes, the movie was given a 16% rating based on 40 reviews.
Roger Ebert gave it a rating of three in a half stars, saying that it "The narrative is very complex, but what's on the screen is little more than generic, non-narrative-specific, guy-being-chased stuff.".
The San Francisco Examiner said the film "...the movie often feels like an attempt by filmmaker Andrew Davis to replicate the massive (and entirely justified) success of 1993's The Fugitive.".