Investigations of adults with a psychoactive substance use disorder (PSUD) or antisocial behavior have reported diminished secretion of the adrenal "stress" hormone, cortisol. Consequently, we determined whether prepubertal sons of PSUD fathers, at high risk for later PSUD, differed from controls on salivary cortisol concentrations before, and after, an anticipated stressor. The roles of problematic behavioral disposition and state anxiety in the cortisol responses were also examined. A significant risk-group x time interaction for salivary cortisol concentrations was found, with high-risk boys secreting less salivary cortisol than controls when anticipating the task. High-risk boys also had significantly higher scores for aggressive delinquency and impulsivity that wholly accounted for the risk-group x time effect on salivary cortisol. Thus, cortisol hyporesponsivity was associated with the dysregulated behaviors prevalent among high-risk boys. The results suggest that cortisol hyporesponsivity could be a "marker" for later antisociality and PSUD.