BACKGROUND: The emergence of Global Health Initiatives (GHIs) has been a major feature of the aid environment of the last decade. This paper seeks to examine in depth the behaviour of two prominent GHIs in the early stages of their operation in Uganda as well as the responses of the government. METHODS: The study adopted a qualitative and case study approach to investigate the governance of aid transactions in Uganda. Data sources included documentary review, in-depth and semi-structured interviews and observation of meetings. Agency theory guided the conceptual framework of the study. RESULTS: The Ugandan government had a stated preference for donor funding to be channelled through the general or sectoral budgets. Despite this preference, two large GHIs opted to allocate resources and deliver activities through projects with a disease-specific approach. The mixed motives of contributor country governments, recipient country governments and GHI executives produced incentive regimes in conflict between different aid mechanisms. CONCLUSION: Notwithstanding attempts to align and harmonize donor activities, the interests and motives of the various actors (GHIs and different parts of the government) undermine such efforts.