Aflatoxins are known to alter the pathogenesis of many infectious diseases, but such effects have not been evaluated in trypanosome infections. The aim of the present work was to assess the effects of aflatoxin B1 on the pathogenesis of Trypanosoma brucei rhodesiense infection using a murine model. Mice fed on 0.50 mg/kg aflatoxin b. wt. were infected with T. b. rhodesiense and compared to trypanosome infected and uninfected aflatoxin-fed controls. The clinical and pathological changes were determined and the quantitative data statistically analysed using standard methods. The results showed that infected aflatoxin-fed mice had pronounced dyspnoea, significantly (P<0.05) reduced survival, extreme emaciation, pronounced macrocytic normochromic anaemia characterized by significantly (P<0.05) reduced red cell count, packed cell volume, haemoglobin levels and significantly (P<0.05) increased mean corpuscular volume compared to controls. Grossly, there were pronounced hydrothorax and ascites while histologically, haemorrhages, thrombosis, embolism, massive peri-vascular inflammatory cell infiltration were observed in the infected aflatoxin-fed mice. Severe anaemia, liver damage, nephritis and pancarditis were the major complicating factors which could have caused reduced host survival. It was concluded that aflatoxicosis aggravated the pathogenesis of T. b. rhodesiense infection in mice, and should therefore be taken into consideration during trypanosomosis control programs.