By late 1980s Uganda was the epicenter of the AIDS epidemic in the world but strong preventive interventions and committed leadership has turned the epidemic round. HIV incidence and prevalence have declined but infection rates remain unacceptably high, making HIV vaccine research a priority. Uganda pioneered the first HIV vaccine trial in Africa but had to overcome ethical, scientific and logistical challenges. Preparation for HIV vaccine evaluation (PAVE) studies started in 1994 involving 3000 subjects followed up for 2 years. Results provided information on HIV vaccines acceptability, behavioral change, prevalence and incidence of HIV and gave indication for future successful HIV vaccine trial. In 1996, preparation for HIV vaccine trial of ALVAC (Clade B) HIV vCP205 to test for safety, immunogenicity and cross-clade reactivity started by building consensus in Uganda and addressing scientific, ethical, social, legal and political issues. The study recruited 40 healthy HIV negative volunteers (20 received the vaccine, 20 controls). The experience and skills gained forms a basis for more HIV vaccine trials and we will draw on this experience, and more trials using ALVAC (Clade A) HIV vaccine in both adults and children are being planned as a follow up.