Peripheral blood mononuclear cells (PBMC) from 117 individuals living on two islands in an area (Dongting Lake) endemic for schistosomiasis japonica in China, and 15 control individuals from a non-endemic area of China, were assessed for antigen-stimulated proliferation against five recombinantSchistosoma japonicum antigens of recognized interest in the development of immunity to schistosomiasis. Two recombinant antigens, paramyosin and 28-kD glutathione-S-transferase, stimulated cellular proliferation (stimulation index ≥ 3·0) in 38·5% and 42·5% of subjects, respectively, a level similar to that induced by a soluble whole parasite extract (51·3%). In contrast, three other recombinant antigens tested-a fatty acid binding protein, 22-kD tegumental membrane-associated antigen, and glyceraldehyde-3-phosphate dehydrogenase-stimulated PBMC proliferation in only 3-8% of subjects. Moreover, we also identified a positive association between the degree of exposure, and cellular proliferation following stimulation with recombinant paramyosin or whole parasite extract. Highly significant differences in antigen-stimulated proliferation were also observed between the two islands, Niangashan and Qingshan. The whole parasite extract stimulated proliferation in 90% of subjects from Niangashan island compared with only 42·1% of subjects from Qingshan island (χ2 = 16·88, P = 0·00004), while glutathione-S-transferase stimulated proliferation in 77·3% of subjects from Niangashan island compared with only 34·7% of subjects from Qingshan island (χ2 = 13·09,P = 0·003). A similar, but not significant, trend was observed for paramyosin and the fatty-acid binding protein. The identification of differential cellular proliferative responses to specific schistosome antigens within an infected human population may have important practical implications for vaccine development against schistosomiasis japonica.