This study examined familial, interpersonal, and intrapersonal factors associated with adolescent drug use from both developmental and etiological perspectives. Retrospective case-control and prospective longitudinal designs were used. A multivariate analysis of variance with repeated measures design was conducted to examine changes over time and differences between groups of adolescents in treatment for alcohol and drug problems, drug-using adolescents not in treatment, and non-drug-using adolescents, on 16 measures of familial, interpersonal, and intrapersonal variables. Significant differences were found between adolescents using drugs (clinical or nonclinical) and those not using drugs and alcohol. No differences were found in any of the variables between clinical adolescents and those using drugs but not in treatment.