The Global Alliance for Vaccines and Immunization (GAVI) is seen as a model for the new Global Fund to Fight AIDS, Tuberculosis and Malaria, to be launched early in 2002. We did an assessment in four African countries to report the experiences of ministries of health and their partners in applying to GAVI for funds to strengthen health systems and for new vaccines. Countries welcomed the introduction of hepatitis B vaccine, safe injection equipment, and the financial support to strengthen immunisation programmes. All reported that the pace of the application process was too rapid. District visits revealed low staffing levels, insufficient transport and fuel, poorly functioning cold chains, and infrequent supervision. Information systems were unreliable, which will be an obstacle to GAVI when monitoring and rewarding improvements in immunisation coverage. Also, the high cost of expensive new vaccines will be difficult to sustain if GAVI funding stops at the end of its 5 year commitment. Our study suggests that applications for support and planning for AIDS, tuberculosis, and malaria control under the new Global Fund, will be more complex and demanding on already over-stretched ministries of health. Further, the rapid onset of activities, coupled with uncertainty about the time-scale of donor commitment, could be problematic. A limited and carefully assessed set of initial activities, focusing on where and how to strengthen existing country systems, is more likely to be successful and could provide useful models for scaling-up to larger programmes in different contexts.