Trypanosomosis is a major impediment to livestock production and economic development in those areas of Africa where it is endemic. Although small ruminants appear to perform better than cattle in various agro-ecological zones, the importance of trypanosomosis has not been extensively investigated in these livestock. This study was designed to investigate the prevalence of trypanosomosis in sheep and goats in an endemic area and to evaluate the performance of different breeds under high tsetse challenge and the potential role of chemoprophylaxis in the control of the disease. The results showed that tsetse flies feed readily on small ruminants, and that these animals are susceptible to trypanosomosis. The Small East African goats acquired fewer infections than the Black Head Persian and Dorper sheep used in the study. In both sheep and goats, chemoprophylaxis with isometamidium chloride (Samorin, Rhone Merieux, Annecy, France) was protective, resulting in fewer infections and higher body weight gain. Trypanosomosis caused anaemia in both sheep and goats, and animals whose PCV fell below 15% rarely recovered, even with trypanocidal drug treatment. The peak transmission period was between 1 and 3 months after the peak tsetse fly density, which raises the possibility of effective strategic prophylaxis.