The present study develops and evaluates a theoretical framework of mediators of the relationship between acculturation and adolescent sexual behavior. Four hundred Latino mother-adolescent dyads from the Bronx, New York were interviewed. The study explored the relationship between intentions to have sexual intercourse and explanatory variables such as adolescent romantic relationship status and partner preferences, maternal approval of dating, adolescent perceptions of maternal approval of dating, and maternal and adolescent levels of familismo and acculturation. Findings revealed complex dynamics between acculturation and adolescent sexual behavior. Protective and risk-inducing associations were observed, with important gender differences operating for boys and girls. Implications for the development of applied prevention programs are discussed.