To compare the characteristics of women and men with Trypanosoma brucei gambiense trypanosomiasis, all 3231 cases treated in Nioki hospital, Democratic Republic of Congo, from 1982 to 2000 were reviewed for demographic information, date and mode of diagnosis, pre-treatment cerebrospinal fluid (CSF) examination, treatment given and its adverse effects, and whether a diagnosis of relapse was made during post-treatment follow-up. Women had a higher apparent incidence of Gambian trypanosomiasis than men (1768 cases in females, 1463 in males), due to selective migration of males out of endemic foci and potentially to a higher exposure among females. Women presented with a less-advanced disease than men: 27% (384/1431) of women had CSF trypanosomes and 72% (1024/1431) had an abnormal CSF white cell count, while corresponding figures in men were 39% (431/1115) and 82% (910/1115) (P < 0.001 for both comparisons), presumably because of differences in health-seeking behaviour. Men (61/718, 8.5%) were more likely to relapse after melarsoprol treatment than women (41/857, 4.8%) (P = 0.004), even after adjustment for other independent risk factors in multivariate analysis. The cause of this higher risk of treatment failure among men treated with melarsoprol remains unclear.