Laboratory examination of blood smears from water buffaloes in an area of high fly challenge indicated an infection rate of 51.11 % caused by both Trypanosoma congolense and T. vivax. A similar study in cattle raised in a low fly challenge area showed an infection rate of 22.73% caused by T. congolense only. Diminazene aceturate administered as a single dose at 3.5 mg/kg body weight cured the infection in cattle, while a similar dose at 7 mg/kg body weight failed to cure the water buffaloes. Cattle were further protected by a single dose of isometamidium chloride administered at 0.5 mg/kg body weight for 6 weeks of this study. On the other hand, isometamidium chloride administered at 1 mg/kg body weight cured transiently 90% of the infected water buffaloes and 10% persisted with a T. congolense infection. It was concluded that the lower dose rates approved by the manufacturers for the two trypanocides treated adequately infected cattle in a low challenge area, but such results were not achieved with the higher dose rates for infected water buffaloes in a high fly challenge area.