Adolescents with substance use problems were classified into four distinct and meaningful subgroups based on patterns of depressive symptoms and motives for drinking before sex (i.e., avoidance, enhancement and social motives) using cluster analysis. Data were collected in face-to-face interviews from 120 adolescents and young adults (87 men, 33 women; mean age = 17.2 years) undergoing substance abuse treatment. Groups with higher and lower functioning were validated via significant group differences in conceptually relevant variables assessing psychological distress, alcohol use behaviors, and HIV-relevant risk behaviors. These analyses identified a subgroup of adolescents with high levels of depressive symptoms and drinking motives who are at elevated risk for HIV/STD exposure due to higher levels of risky sexual behavior and altered sexual behavior related to co-occuring alcohol use. Implications for morbidity, mortality and treatment effectiveness in this at-risk sample are discussed.