An inhibition enzyme-linked immunosorbent assay (IELISA) was used to detect the presence of schistosome antigens obtained from cercariae, adult worms, and eggs of the parasite. Using appropriate titers of Schistosoma mansoni infected mouse serum (IMS), it was possible to detect less than 10 ng/ml of schistosome antigen when added to phosphate-buffered saline (PBS, pH 7.2) or normal human serum (NHS). The sensitivity of the test was highly contingent on the number of experimental variables including antibody titer and antigenic source. The results of specificity studies were complicated. Although there was no cross-reactivity detected with other unrelated antigen preparations, extensive cross-reactivity between various schistosome species and "stage-specific" antigens was observed. The IELISA, utilizing IMS, can quantitate the degree of antigenic cross-reactivity, i.e., genus-specific and cross-reacting antigenic determinants. Soluble egg antigen (SEA) preparations obtained from S. mansoni and S. japonicum actually "cross-reacted" more than cercarial- and egg-derived antigens obtained from the same species (S. mansoni). This test also showed a 32-fold increase in specificity for the quantitative detection of specific antigenic determinants when monoclonal antibodies were used to restrict the heterogeneity of the measured response. The technique proved satisfactory for the quantification of parasitic burden in mice and the detection of active infections in humans. Circulating antigen disappeared with a t 1/2 of 72-96 hr after successful treatment.