Selected family variables, especially maternal behaviors, were studied as predictors of alcohol and drug misuse in severely disturbed adolescent boys from largely father-absent homes. The families of 50 male youths (mean age 15.8 years) in a residential center for alcohol and substance misuse were compared with the families of a community control group (mean age 16.3 years). Within-subject group comparisons also were made. Family structure, interactive processes, maternal and paternal alcohol and substance use, and criminality were assessed through direct interview and/or self-report. The families of alcohol- and substance-misusing boys were markedly disadvantaged or impaired on numerous family structure, process, and substance-misusing behavioral variables in comparison with community controls. Within the alcohol- and substance-misusing group itself, family process variables, maternal alcohol symptoms, and maternal criminality differentiated boys with more vs. less severe drug-dependence symptoms. Maternal alcohol problems and criminality were more important than family process variables. Paternal alcohol or substance misuse or criminality did not differentiate proband symptom severity. We concluded that maternal alcohol symptoms and criminality differentiate severity of drug dependence in severely disturbed, substance-misusing adolescent males from largely father-absent homes. Maternal substance misuse should be evaluated carefully in adolescent substance abuse treatment settings.