The authors examined gender differences in rates of comorbid psychiatric disorders among adolescents with 1 or more psychoactive substance use disorders. Baseline diagnostic data were obtained from 135 adolescents, ages 12 to 19, and their parents-guardians, who participated in a study to develop and efficacy test Integrated Family and Cognitive-Behavioral Therapy. Rates of attention-deficit/hyperactivity disorder and conduct disorder were higher among drug-abusing male adolescents compared with drug-abusing female adolescents. However, high rates of disruptive behavior disorders also characterized drug-abusing female adolescents. Similarly, drug-abusing female adolescents exhibited a higher rate of major depression compared with drug-abusing male adolescents. However, rates of dysthymia, double depression (i.e., major depression and dysthymia), and bipolar disorder were equivalent between genders.