Past research has shown that recreational drug use correlates with sexual behaviors that confer high risk for human immunodeficiency virus (HIV) infection. The present study tested the hypothesis that sensation seeking, a disposition characterized by the tendency to pursue novel, exciting, and optimal levels of arousal, accounts for a majority of the variance in associations between substance use and high-risk sexual behavior. Ninety-nine homosexually active men completed measures of sensation seeking, self-reported sexual behavior, and substance use. Path analysis and hierarchical regression analyses demonstrated that sensation seeking accounts for the observed relationship between substance use and high-risk sexual behavior. We conclude that personality characteristics, often ignored in high-risk sexual episodes, predict risk behavior over and above substance use, and may be useful in tailoring HIV prevention interventions.