Given the scale and severity of AIDS in South Africa, and (until recently) the highly contested policy environment of a government in denial about the casuality of HIV and AIDS, bilateral and multilateral overseas development assistance donors have come to play a critical role in the shaping of AIDS policy in terms of its formulation, implementation and evaluation. In the contexts of debates regarding the effectiveness of aid in global health, one measure of such effectiveness is its impact on the domestic policy agenda. In the first half of 2007 we conducted 30 interviews with key AIDS donors and civil society partners in South Africa. This ethnographic study provides an analysis of these respondents' views regarding their role in the AIDS policy process - in particular as they work towards a change in the policy agenda. The analysis is guided by John Kingdon's multiple streams framework, which explains policy change in terms of agenda-setting. The findings illustrate the interplay between domestic and international actors in the context of global health assistance and provide a rich insider's perspective on the machinations around agenda-setting. The article concludes that national-level politics was the most fundamental impediment to real effectiveness in South Africa AIDS policy in the period up to 2008.