This study investigated the convergence of temperament dimensions with constructs from C. R. Cloninger's (1987a) theory using data from a sample of 949 adolescents (M age = 13.6 years). Substantial convergence was found, and both types of constructs were related in predicted ways to self-regulation variables and adolescent substance use. Structural modeling procedures tested a mediational model for substance use; results showed mediation through self-control, academic competence, negative life events, and deviant peer affiliations. Interactions indicated that substance use could be predicted from a balance of systems for good control and poor control. Poor self-control was present for dimensions implicated in both externalizing and internalizing disorders. Results are discussed with reference to self-regulation models of substance use and the comorbidity of substance abuse and mental disorder.