Peer-led programs that employ classroom-based group exercises have been shown to be the most effective in preventing adolescent tobacco use. In addition, health promotion programs that include cultural referents have also been shown to be advantageous. The purpose of this study was to test the interaction between the method by which leaders and peers are assigned to cooperative groups and the cultural relevance of the curricular materials. Sixth-grade students were randomly assigned to one of three group assignment conditions (random, teacher and network) and one of two anti-tobacco curricular programs (universal and culturally-specific). Follow-up data on 1235 7th grade students in 14 schools were used to evaluate the program's effectiveness. Results indicate that the interaction between the network condition and culturally-relevant curriculum most significantly reduced the likelihood of 7th grade smoking (OR=0.32, p less than 0.01). The primary conclusion is that peer-led health promotion programs not only have to consider the selection of peer leaders and the assignment of students to those leaders, but also the cultural relevance of the curricular materials. This study supports the view that social networks influence behavior and that network-based information along with culturally relevant curricular materials can be used to increase program effectiveness. (Contains 3 tables.)