Like many behavioral phenotypes, generalized vulnerability to substance dependence in adolescence has a complex etiology; it is influenced by both genetic and environmental risks, with a heritability of approximately 0.40 [Button, T.M., Hewitt, J.K., Rhee, S.H., Young, S.E., Corley, R.P., Stallings, M.C., 2006. Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence. Twin Res. Hum. Genet. 9, 38-45]. However, the extent to which the magnitudes of genetic and environmental risk for substance dependence are contextually moderated is unclear. The aim of the current study was to determine whether the etiology of substance dependence vulnerability (DV; total lifetime symptom count of dependence criteria endorsed across numerous substances divided by the number of substances used) varies depending on the extent of affiliation with delinquent peers as perceived by the adolescent. Results show that affiliation with delinquent peers moderates both the unstandardized (absolute) and the relative contribution of genetic, shared, and non-shared environmental risks to the variance of DV. The genetic variance was estimated to be higher among subjects who perceived their peers to be least delinquent and among those who considered their peers to be the most delinquent. The magnitudes of both shared and non-shared environmental influences were negligible among those who perceived their peers to be least delinquent and were greater among those with higher levels of perceived peers' delinquency.