Schistosomula of Schistosoma mansoni, recovered either after penetration of cercariae through isolated rat skin or by mechanical transformation of cercariae, become fully resistant after 24–48 h of culture to damage by human blood eosinophils in the presence of human anti-schistosomular sera. Cultured schistosomula are also shown to lose their susceptibility to attack by human eosinophils in the presence of human complement. This resistance is related to the simultaneous reduction of the ability of human anti-schistosomular antibodies and human complement component C3 to bind to the surface of the cultured larvae. The development of insusceptibility to antibody, complement and eosinophil-mediated attack does not require the acquisition by the schistosomula of a protective coat of host or other macromolecules, since it is achieved in chemically defined culture medium free of serum and macromolecules. This supports the hypothesis that schistosomula undergo intrinsic changes which render them insusceptible to immune attack.