The spectrum of clinical manifestations of trypanosomiasis in south-eastern Uganda is extremely wide. Isoenzyme characterization of trypanosome strains isolated in this area during recent epidemics of sleeping sickness has shown that particular clinical features of the disease can be related to the zymodeme of the causative parasite. For example, B17, part of the 'busoga' group of isolates and a zymodeme identified from central areas of Busoga during outbreaks of sleeping sickness, is associated with severe early features and a high frequency of presentation with a chancre. Isolates belonging to the 'zambezi' group, most of which came from areas close to the lake shores or close to the River Nile, were more heterogenous and were associated with significantly different clinical features: a more chronic, prolonged illness; more frequent presentation with meningo-encephalitis, and less frequent chancres. The clinical spectrum of infection associated with the parasites currently in circulation indicates that the previous endemicity and the early epidemics could be explained on the basis of existing zymodemes.