A high-risk (HR) group of adolescents having fathers with a lifetime diagnosis of a psychoactive substance abuse disorder was compared with a low-average-risk (LAR) group whose fathers did not have psychoactive substance abuse disorder. Executive cognitive functioning (ECF) and behavioral activity were measured using neuropsychological tests, activity monitor, diagnostic interview, and informant ratings when the subjects were 10 to 12 years of age. Alcohol, tobacco, and cannabis use was measured at 2-year follow-up. At baseline, the HR group had a significantly higher behavioral activity level and poorer performance on ECF tests. By early adolescence, HR subjects had a higher lifetime rate of tobacco and cannabis use and earlier age at onset of cannabis use. ECF capacity, but not behavioral activity level, predicted tobacco and cannabis use, total number of drugs ever tried, and severity of drug involvement. ECF accounted for additional variance beyond the effects of conduct problems on these outcomes. Tables, references