The adolescents (n=140, 54 percent female, and 15.9 years average age) met DSM-III-R criteria for a substance-use disorder and at least 1 other Axis I psychiatric disorder. Interviews were conducted independently with each adolescent and parent, using a different trained interviewer for each parent and adolescent. The interviews yielded information on demographics, social and academic functioning, family history of alcohol and drug use and problems, physical and emotional health, and previous treatments. In addition to having multiple psychiatric disorders, the adolescents reported extensive alcohol and other drug involvement. The highest rates of drug dependence were for marijuana (82 percent), alcohol (80 percent), amphetamines (51 percent), and hallucinogens (31 percent). Most of the sample (88 percent) regularly smoked cigarettes. Sixty-one percent of the sample met DSM-III-R dependence criteria for three or more substances. Ages of onset of both Axis I mental health and substance-use disorders were compared to determine the chronological sequencing of disorders. Associations between type of psychopathology and selectivity of substance involvement were first examined by correlations between type of substance use and the presence of individual psychiatric disorders. In addition, differences in type of substance use were compared across broader diagnostic categories. To further test for substance selectivity, the study examined whether there were differences in dependence symptoms, withdrawal symptoms, and substance-related problems across mental health diagnostic groups. As hypothesized, the externalizing conduct disorder (CD) and oppositional defiant disorder (ODD) were selectively associated with the use of cigarettes, alcohol, and stimulants; however, different patterns of associations occurred when the primary/secondary nature of disorders was taken into account. Primary internalizing disorders and primary substance-using disorders were present for youth who demonstrated greater use of barbiturates. The hypothesis that the severity of substance involvement would be related to the intensity of mental health problems of adolescents was supported only for externalizing and depressive disorders. The findings of this study point to the importance of early detection of mental health disorders and substance use disorders among adolescents. 4 tables and 39 references