This study tested derivations from Cloninger's (1987a) theory of substance use on a sample of 457 adolescents. A 67-item adaptation of the Tridimensional Personality Questionnaire (TPQ) and measures of 10 related constructs were administered together with measures of tobacco, alcohol, and marijuana use. Factor analysis indicated that the TPQ comprised nine subscales. An interaction for TPQ dimensions indicated that substance use was particularly elevated for persons with high novelty seeking, low harm avoidance, and low reward dependence. TPQ scales converged with constructs from other theoretical systems, being correlated with measures of behavioral undercontrol, risk taking, impulsiveness, anger, independence, life events, tolerance for deviance, and sensation seeking. Implications for substance abuse theory are discussed.