The analysis correlates and combines findings from epidemiological studies examining the incidence of drugs in various subpopulations of drivers and includes a search of the literature between 1984 and 1992 relating to psychomotor performance and drugs. The article focuses on studies addressing the interaction between drugs and between drugs of abuse and alcohol. Following a preliminary examination of the general mechanisms of drug reactions and the best-known types of interaction among classes of psychoactive substances, the article discusses the more complex problem of pharmacological interaction. Finally, the article covers some issues of methodology, particularly as they relate to epidemiology, man- machine interaction, and the role of the toxicology laboratory. 17 tables, 40 figures, and 225 references