This exploratory study examined gender differences in the patterns of drug offers among a sample of 71 American Indian middle school students. Participants responded to an inventory of drug-related problem situations specific to the cultural contexts of Southwestern American Indian youth. They were asked to consider the frequency of drug offers from specific groups in their social networks and the difficulty associated with refusing drugs from various offerers. The results indicated that female and male American Indian youth differ in the degree of exposure to drug offers and the degree of perceived difficulty in handling such offers. Even after controlling for differences in age, grade level, socioeconomic status, family structure, and residence on a reservation, girls reported significantly more drug offers from friends, cousins, and other peers than did boys. Compared to boys, girls also reported a significantly higher sense of difficulty in dealing with drug offers from all sources. (Contains 4 tables and 1 figure.)