The major source of material for Silkwood was a result of extensive research done by two producers, Larry Cano and Buzz Hirsch. This was highly sensitive information at the time. The Silkwood trial was in its infancy, and Kerr-McGee attempted to subpoena all interview notes, tape recordings, and other Silkwood research documents from the producers. Hirsch refused, even risking jailtime, and his resistance eventually led to a new law allowing filmmakers the same rights (under the First Amendment) as journalists to protect their confidential sources. Still, the film's content was somewhat restricted, since the filmmakers did not want to deal with charges of libel or other legal problems.

The two most important books on Karen Silkwood, Who Killed Karen Silkwood? by Howard Kohn and The Killing of Karen Silkwood by Richard Rashke, were published months apart in 1981. It is possible that these books were sources for screenwriters Alice Arlen and Nora Ephron. Incidentally, Nora Ephron went on to write scripts for When Harry Met Sally, Sleepless in Seattle, and You've Got Mail, among others. This interest in the genre of romantic comedies might account for some omissions and/or inaccuracies in the relationship between Karen Silkwood and Drew Stephens in the film, making them follow a more traditional course.

Most of the film's clashes with fact are a result of time constraints, and some characters and events have been compressed. For example, one of Karen's most important discoveries, the missing plutonium (MUF), is given only a minute or two of discussion in the lunchroom. The biggest problem with the film's use of history is that there isn't enough of it, causing the film to be both less accurate and less entertaining, since some events lose their significance or simply don't make sense. The viewer does not have enough background on Karen, nor enough knowledge of her character to understand why she does what she does. The Drew-Dolly-Karen household is misrepresentative of Karen's actual living situation, and Dolly is a combination of at least two real people.

Possibly the most unexplored event in the film is the accident scene, which suggests that Karen was murdered but gives no details about the accident except for the car's final resting place.