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Sera from patients with acute and chronic schistosomiasis mansoni, and from laboratory-infected monkeys, were examined by an enzyme-linked immunosorbent assay technique using antigens prepared from eggs, cercariae, and adult worms. Sera from patients with acute schistosomiasis and from monkeys 2 months post-infection reacted more positively to cercarial antigen than to adult worm antigen whereas sera from both patients with chronic schistosomiasis and monkeys infected for longer than 4 months reacted more positively to adult worm antigen. These differential responses to antigen serologically differentiated between acute and chronic schistosome infections.