Describes (a) the effects of a social-influences-based drug prevention program (the Midwestern Prevention Project) on the mediating variables it was designed to change and (b) the process by which the effects on mediating variables changed use of drugs (tobacco, alcohol, and marijuana). Students in 42 middle schools and junior high schools in Kansas City, Missouri, and Kansas City, Kansas, were measured in the fall of 1984 (N = 5,065) and again 1 year later (N = 5,008) after 24 of the schools had been through the program. Compared to students in control schools, students in program schools became less likely to express belief in the positive consequences of drug use, less likely to indicate that they would use such drugs in the future, more likely to report that their friends were less tolerant of drug use, and more likely to believe that they were better able to communicate with their friends about drug or school problems. Change in perceptions of friends' tolerance of drug use was the most substantial mediator of program effects on drug use. There was evidence that intentions to use and beliefs about the positive consequences of use may also mediate program effects on drug use.