Aims: This longitudinal study investigated person-environment interactions and adolescent substance use by examining whether, and if so how, early temperamental quality of sensation seeking interacted with current neighborhood characteristics to shape underage smoking, drinking, and marijuana use. Sample: Participants consisted of a community-representative sample of 352 adolescents. Methods: Early temperament was assessed when adolescents were between seven and 13 years of age, and current neighborhood characteristics (as perceived by participants and their mothers) and current adolescent substance use (self-reported smoking, drinking, and marijuana use in the past 30 days) were assessed approximately three years later. Results: The results from a zeroinflated negative binomial (ZINB) regression revealed a potent negative effect of the perceived neighborhood risk, such that riskier neighborhoods were associated with both a greater probability for any substance use among adolescents, and a greater frequency of substance use among those who were engaging in these behaviors. High sensation seeking was a risk factor only for frequency of substance use among adolescent extant users, but not for the likelihood of any use. In addition, a significant interaction between sensation seeking and neighborhood risk revealed that adolescent sensation seekers engaged in smoking, drinking, and marijuana use primarily under conditions of elevated neighborhood risk and increased opportunity for such behaviors. Conclusion: Underage substance use was affected by synergistic effects between personal and community risk factors.