Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals insouth-east Uganda were studied for susceptibility to diminazene, isometamidium andmelarsoprol in vitro. All stocks were susceptible to melarsoprol. One T. b. rhodesiense stockisolated from a sleeping sickness patient showed reduced susceptibility to the veterinarydrugs diminazene and isometamidium. More than 100 ng/ml diminazene or 0.78 ng/mlisometamidium were required to eliminate that stock during 10 days drug exposure. Incontrast, the remaining stocks were eliminated by 0.8–6.3 ng/ml diminazene and0.01–0.20 ng/ml isometamidium. Clones derived from the resistant T. b. rhodesiense stockshowed reduced susceptibility to isometamidium and diminazene comparable to the parentalpopulation. Control of sleeping sickness by treatment of the animal reservoir could,therefore, face serious problems since drug-resistant stocks as reported here would mostlikely not be eliminated by recommended doses of diminazene and isometamidium.