The development of hepatosplenic schistosomiasis in humans cannot always be related to the intensity of infection. A study was designed to identify different humoral immunologic responses to Schistosoma mansoni in patients with and without hepatosplenic disease. Twenty-four patients with active hepatosplenic disease were closely matched for age, sex, and fecal egg counts with twenty-four patients with only intestinal disease. A serum sample from each of these patients was tested for antibodies to the major soluble egg antigen (MSA1) by radioimmunoassay, for total and IgM antibodies to egg and worm antigenic preparations by ELISA, and for its ability to suppress antigen stimulated lymphocyte blastogenesis. No difference was found using these assays between the hepatosplenic and the intestinal schistosomiasis patients.