In order to preliminarily evaluate the efficacy, safety and tolerability of the serotonin reuptake inhibitor, sertraline, in the treatment of adolescents with a primary depressive disorder and a comorbid alcohol use disorder, a 12-week double-blind, placebo-controlled trial of sertraline plus cognitive behavior group therapy was conducted. Subjects were 10 outpatient treatment-seeking adolescents. Baseline assessment included the K-SADS, HAM-D, SCID, and the Time-Line Follow-Back. The HAM-D and the Time-Line Follow-Back were performed weekly thereafter. Both groups showed a significant reduction in depression scores with an average reduction between baseline and endpoint HAM-D score of -9.8 (F(1,8)=26.14, p</=0.001), although there were no significant group differences. There was an overall reduction in Percent Days Drinking (PDD); (F(1,8)=8.90, p<0.02) and in Drinks Per Drinking Day (DDD); (F(1,8)=20.48, p<0.002), however, there were no group differences. Depression responders tended to have higher baseline PDD than non-responders (F(1,8)=3.9, p=0.08) and change in HAM-D scores tended to correlate with change in PDD (r=0.57, p=0.09). Our data support that sertraline is safe and well tolerated in the treatment of adolescents with depression and alcohol dependence. Small sample size and cognitive behavior group therapy given to all subjects may limit the lack of group differences. Copyright 2000 John Wiley & Sons, Ltd.