The aim of this study was to assess the presence of alcohol, illicit drugs and medicinal drugs among Spanish drivers involved in fatal road accidents between 1991 and 2000. Samples were obtained for 5745 drivers killed in road accidents from January 1991 to December 2000. Of the samples, 91.7% represented males and 8.3% females; 40.7% were under 30 years of age, 31.9% were under 31-50 years of age, 19.5% were over 51 years of age, and for 7.9% the age was unknown. Between 1991 and 2000, some type of psychoactive substance was detected among 50.1% of those drivers killed in road accidents, this being mainly alcohol (43.8%) and, less frequently, illicit drugs (8.8%) and medicinal drugs (4.7%). In all the cases, in which alcohol was detected, combined use with other substances accounted for only 12.5%, whilst in the case of illicit and medicinal drugs, figures representing combined use with other substances were 75.6% for the former and 65.8% for the latter. For one in every three cases (32.0%), a blood alcohol level over 0.8 g/l was recorded; cocaine (5.2%), opiates (3.2%) and cannabis (2.2%) were the three illicit drugs most frequently detected. Among medicinal drugs, were benzodiazepines (3.4%), anti-depressant drugs (0.6%) and analgesics (0.4%). The results show the frequent presence of psychoactive substances, particularly alcohol, among Spanish motor vehicle users involved in fatal road accidents. It should be pointed out that illicit and medicinal drugs in combination with other substances were a common feature. #