The effect of neonatally initiated injections of anti-mu serum on immunity to reinfection with Schistosoma mansoni in the rat was investigated in vitro and in vivo. Anti-mu treatment resulting in a profound depression of immunoglobulin synthesis dramatically decreased immunity to reinfection assessed by worm recovery technique. Complement-dependent antibody, IgG2a antibody-eosinophil-mediated and IgE-macrophage cytotoxicity reactions were in parallel markedly reduced. These results show the prominent role played by antibody-dependent mechanisms in immunity to schistosomes in the rat.