Cytokine responses of peripheral blood mononuclear cells from humans infected with Schistosoma mansoni were assessed. By ELISA and ELISPOT, persons with acute and hepatosplenic infections produced higher levels of interleukin (IL)-4 and IL-5 and higher frequencies of IL-4-producing cells in response to mitogen than did uninfected persons. In contrast, mitogen-induced production of the Th1 cytokine interferon-gamma (IFN-gamma) did not differ from that of uninfected controls. Upon stimulation with egg antigens, many patients responded with elevated IL-4 mRNA levels but displayed no appreciable increases in Th1 (i.e., IFN-gamma and IL-2) cytokine transcripts. Nevertheless, in cells stimulated with adult worm antigen, a more mixed Th0-type response was observed with production of both Th1 and Th2 cytokines. These results support previous findings in laboratory mice that schistosome infection results in increased production of Th2 cytokines. Unlike mice, infected humans do not display a generalized down-modulation in Th1 responses but instead show a selective deficiency in IFN-gamma and usually IL-2 responses to egg antigens.