BACKGROUND: In East Africa, visceral leishmaniasis (VL) is endemic in parts of Sudan, Ethiopia, Somalia, Kenya and Uganda. It is caused by Leishmania donovani and transmitted by the sandfly vector Phlebotomus martini. In the Pokot focus, reaching from western Kenya into eastern Uganda, formulation of a prevention strategy has been hindered by the lack of knowledge on VL risk factors as well as by lack of support from health sector donors. The present study was conducted to establish the necessary evidence-base and to stimulate interest in supporting the control of this neglected tropical disease in Uganda and Kenya. METHODS: A case-control study was carried out from June to December 2006. Cases were recruited at Amudat hospital, Nakapiripirit district, Uganda, after clinical and parasitological confirmation of symptomatic VL infection. Controls were individuals that tested negative using a rK39 antigen-based dipstick, which were recruited at random from the same communities as the cases. Data were analysed using conditional logistic regression. RESULTS: Ninety-three cases and 226 controls were recruited into the study. Multivariate analysis identified low socio-economic status and treating livestock with insecticide as risk factors for VL. Sleeping near animals, owning a mosquito net and knowing about VL symptoms were associated with a reduced risk of VL. CONCLUSIONS: VL affects the poorest of the poor of the Pokot tribe. Distribution of insecticide-treated mosquito nets combined with dissemination of culturally appropriate behaviour-change education is likely to be an effective prevention strategy.