Numerous pharmacological agents have been shown to have powerful effects on cognitive behavior. Schizophrenia-like reactions have been reported in some instances. There have also been persistent reports of drug abuse among psychiatric patients before and during hospitalization. These phenomena have led to speculation that psychoactive substances are affecting the course and outcome of psychiatric illnesses, and in particular, schizophrenia. This report first reviews the evidence for psychotomimetic effects of various drugs, and then focuses on reports of the effect that substance abuse has on the course of schizophrenia and long-term outcome. The evidence to date indicates that there is a need for a large epidemiological analysis of the interplay between drug abuse and schizophrenia as well as more intensive case studies of afflicted individuals. This discussion concludes with suggestions for improved research methods and two designs for future investigations.