The progression of humoral immune responses exhibited by mice during the year following exposure to Schistosoma mansoni cercariae was established by studying radioimmunoprecipitations of adult male and cercarial glycoproteins. 35S-methionine metabolically-labeled adult S. mansoni male worm glycoproteins precipitated by sera of 14 mice were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The initial specific antibody response (week 5) was directed against 3 worm glycoproteins of 55,000, 52,000 and 35,000 molecular weight (Mr). As infection progressed, all major worm glycoproteins (ranging from 400,000 to 12,000 Mr) were precipitated by sera from each mouse and only minor individual variations in titer were noted in the antibody responses of the mice against these glycoproteins. Maximal immunoreactivity toward the radiolabeled glycoproteins occurred at week 20 and remained at this level through week 50. Analogous experiments with sera from acutely- and chronically-infected humans resulted in immunoprecipitation patterns almost identical to those obtained with sera from the corresponding experimentally-infected mice. The kinetics of the antibody response against 125Iodine-labeled cercarial glycoproteins was the same as that observed with worm glycoproteins.