BACKGROUND: Psychomotor studies suggest that psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road traffic accidents (RTA). METHODS: We carried out a case-crossover study of drivers >18 years, resident in Tayside, Scotland, and who experienced a first road traffic accident recorded by Tayside Police between 1 August 1992 and 30 June 1994. Each driver had used one of the following drugs: tricyclic antidepressant (TCA), selective serotonin reuptake inhibitor (SSRI), benzodiazepines or other psychotropics, between 1 August 1992 and the date of RTA. For each driver, the probability of having the RTA whilst exposed to a drug was compared with the probability whilst unexposed. RESULTS: Of 19,386 drivers with a first RTA during the study period 1,731 were users of any study drug. On the day of the accident, 189 subjects were taking TCAs, 84 were taking selective SSRI, 235 were taking benzodiazepines and 47 were taking other psychoactive drugs. The within patient exposure relative risks were 0.93 (95% CI: 0.72-1.21) for TCAs, 0.85(0.55-1.33) for SSRIs, 1.62 (1.24-2.12) for benzodiazepines and 0.88(0.62—1.225) for other psychotropics. The benzodiazepine risk decreased with increasing age of driver and was increased in subjects with a positive breath test for alcohol. A dose-response relationship was evident with benzodiazepines, the relative-risk increasing with dose. CONCLUSION: Users of benzodiazepines were at increased risks of experiencing a road traffic accident, however users of TCAs and SSRIs were not. Users of benzodiazepines should not drive.