The present study investigated the comorbidity of alcohol and drug dependence with psychiatric disorders by gender in a clinical sample of 300 girls and 208 boys (age 12-17) admitted to psychiatric inpatient hospitalization between April 2001 and March 2006. Information on alcohol and drug dependence, psychiatric diagnoses and age at onset of these disorders was obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children--Present and Lifetime. The results of logistic regression models revealed that behavioral disorders were associated with alcohol dependence among girls (odds ratio [OR] 7.1) and boys (OR 4.6). In addition, behavioral disorders were associated with drug dependence, the ORs being 18.4 in girls and 9.1 in boys. Although depressive disorders were associated with both alcohol (OR 3.1) and drug dependence (OR 3.8) among boys, no corresponding association was seen in girls. Our results suggest that physicians treating substance-dependent adolescents should focus not only on behavioral disorders, but also on the screening and treatment of underlying depressive disorders, especially among substance-dependent boys.