The study was designed to assess the relative effects of various factors on initiation to drug use and to provide underlying guidelines for a school-based educational prevention program. A total of 1,900 Israeli adolescents, males and females, were involved in the study. The longitudinal research design permitted the identification of adolescents initiated into the substance using group and also singled out the variables that contributed most to the initiation. Results indicate that the likelihood of substance use among Israeli adolescents increases as a function of positive attitudes toward drugs, substance use, and substance users; positive attitudes ascribed to peers and parents; peers and parents use of alcohol and drugs; personality variables such as sensation-seeking and anxiety-state; and availability of the drugs at home and in the community. The prevention program designed from these findings includes phases on the clarification of values and attitudes, information on drugs and services, a substance-temptation-inoculation workshop, alternative modes of satisfaction, and parental involvement. Teacher training for the course is briefly outlined. 35 references.