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Cellular and humoral immune responses to soluble egg antigens (SEA) were studied in the course of Schistosoma mansoni infection in the hamster. No immune response to SEA could be detected before the parasite had started oviposition. The liver granuloma size reached a maximum 6 weeks after infection and decreased rapidly thereafter. The in vitro cell-mediated immune response to SEA (lymphocyte blast transformation) showed a maximum reaction 12 to 16 weeks after infection (depending on the infection rate) and also declined later. Parallel to the lowered reactivity of the lymphocytes to SEA in vitro, responsiveness to the nonspecific T-cell mitogen, phytohemagglutinin M, was also reduced in chronic infections. Humoral anti-SEA antibodies could be detected in increasing amounts up to 10 weeks after exposure.