Older drivers have the second highest risk for motor vehicle collisions of any age group, after adolescents. Psychoactive medications may place older drivers at increased risk for injurious motor vehicle collisions. We conducted a population-based matched case-control study of older drivers who were involved in injurious crashes during 1987 and 1988. The 234 cases and 447 controls were members of a large Seattle-based health maintenance organization. Use of anti-depressants and opioid analgesics by older drivers was associated with increased risk for injurious motor vehicle collisions. Compared with non-users, current users of cyclic antidepressants had an adjusted relative risk (RR) of 2.3 [95% confidence interval (CI) = 1.1-4.8]. Opioid analgesic use was also associated with an elevated crash risk (adjusted RR = 1.8; 95% CI = 1.0-3.4). We found no evidence of a dose-related effect with either class of drug. Current use of benzodiazepines or sedating antihistamines had little association with increased risk for injurious collisions.