This paper examines the processes for building highly collaborative public-private partnerships for public health, with a focus on the efforts to manage the complex relationships that underlie these partnerships. These processes are analyzed for the African Comprehensive HIV/AIDS Partnerships (ACHAP), a 5-year partnership (2001-2005) between the government of Botswana, Merck & Co., Inc. (and its company foundation), and the Bill & Melinda Gates Foundation. ACHAP is a highly collaborative initiative. The ACHAP office in Botswana engages intensively (on a daily basis) with the government of Botswana (an ACHAP partner and ACHAP's main grantee) to support HIV/AIDS control in that country, which had an adult prevalence of 38.5% HIV infection in 2000 when ACHAP was being established. The paper discusses the development of ACHAP in four stages: the creation of ACHAP, the first year, the second and third years, and the fourth year. Based on ACHAP's experiences over these four years, the paper identifies five lessons for managing relationships in highly collaborative public-private partnerships for public health.