Cellular immune responses to schistosomal antigens were examined in 110 Schistosoma haematobium-infected individuals before and 5 weeks after treatment with praziquantel. Chemotherapy resulted in significant decrease in worm load as measured by egg output and circulating antigens. The proliferative responses to adult worm antigen (AWA) increased significantly after treatment (p < 0.001) whereas purified protein derivative of tuberculin or phytohemagglutinin responsiveness was unaffected. Interleukin (IL)-4 production in response to both AWA and soluble egg antigen (SEA) increased markedly after treatment (p < 0.001), but IL-5 remained unchanged. None of the studied subjects released any measurable IL-2 and only 21% produced interferon (IFN)-gamma in response to parasite antigens. The deficiency in either IFN-gamma or IL-2 release was not restored by chemotherapy. Thus chronic infection with S. haematobium is associated with the reversible down-regulation of T cell proliferative responses and IL-4 release. Results from cell depletion experiments indicated that CD4+ T cells were the target of this down-modulation.