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This study examined predictors of methamphetamine use in a 6-month prospective study of 2,270 rural young adults. Sensitivity to punishment (SP), sensitivity to reward (SR), and gender were exogenous variables in an observed variable path analysis with 3 endogenous criteria: Time 1 (T1) marijuana use and methamphetamine use at T1 and Time 2 (T2). SP was negatively associated with marijuana use at T1, and this association was attenuated by SR. Male gender was positively associated with marijuana use. T1 marijuana use and SR were positively, and male gender negatively, associated with T1 methamphetamine use. T1 methamphetamine use, T1 marijuana use, and SP were positively associated with T2 methamphetamine use. Methamphetamine use prevalence and the role of distal predictors and proximal indicators of drug involvement are discussed.