In order to investigate whether protective immunity appears after Trypanosoma brucei gambiense sleeping sickness, we undertook a retrospective cohort study of 3 remote villages in central Zaire (total population 1431), in which 38% of all adults had a past history of human African trypanosomiasis. Among adults previously diagnosed with trypanosomiasis and treated, the risk of a second episode of trypanosomiasis during the 10 years period of observation was only 15% (with a 24 months refractory period) and 30% (without a refractory period) of the risk of a first episode in adults never previously diagnosed. We could not demonstrate a similar difference among children, to some extent because only a few of them were diagnosed for a first time with trypanosomiasis. Our findings suggest that very significant immunity appears after Gambian sleeping sickness, and that developing a vaccine against this subspecies of trypanosomes is biologically plausible.