Combining substance use and sex compounds the risk of contracting sexually transmitted diseases, including HIV. However, the association between substance use and sexual behaviors may vary by substance and sexual behavior. The current study sought to examine the relationship between alcohol and marijuana use frequency and specific sexual behaviors. The International Longitudinal Survey of Adolescent Health was administered to 1432 youths in one middle school and one high school in Minnesota. Results from logistic regression analyses indicated a relationship between alcohol and marijuana use and being sexually active. However, only marijuana use was associated with having multiple partners. To aid researchers in designing more effective HIV prevention interventions, future research should focus on understanding the differential effects of alcohol and marijuana on sexual behaviors. (Contains 4 tables.)