Previous research examining relationships between parental monitoring, friendship networks, and substance use did not take into account the gender of both the adolescent and the friends. The goal of this study was to test a mediation model in which having other-sex friends during mid-adolescence mediates the relationships between parental monitoring in early adolescence and substance use during late adolescence. The authors hypothesized that mediation would be observed for girls but not for boys. A sample of 333 adolescents (60 percent girls) was surveyed yearly from ages 12 to 19. The findings provided support for an indirect relationship (mediation via other-sex friendships) between early adolescent parental monitoring and late adolescent alcohol use among girls only. That is, for girls, higher levels of parental monitoring lead to fewer other-sex friendships, which then lead to lower levels of subsequent alcohol use. For drug use, the findings provided support for a direct relationship between early adolescent parental monitoring and late adolescent drug use for both boys and girls. Thus, parents seem to have a protective effect on their daughters' later use of alcohol by limiting inclusion of male friends in their networks. Abstract published by arrangement with Springer.