Through cross-disciplinary and participatory processes involving key stakeholders from the Zambian education sector, as well as from the traditional leadership structure, a localized HIV/AIDS-prevention strategy, Interactive School and Community Approach (ISACA), was developed and implemented throughout one province between 2002 and 2006. The study is guided by constructivist grounded theory and explores the impact of the chiefs' involvement in preventing the spread of HIV/AIDS through close collaboration and interaction across traditionally vertical boundaries, for example between the formal educational and traditional leadership structures. The strategy created communicative spaces for the merger of Western and indigenous knowledge. The study reveals the importance of involving the chiefs, the custodians of culture and traditions in cultural transformation and development, and shows their significant role as gate-openers and change agents, a precondition for sustainable local development. (Contains 2 figures.)