Mice of various inbred strains differ markedly in resistance to first infection with Taenia taeniaeformis. Hypothymic nude mice of relatively resistant (e.g. BALB/c) and relatively susceptible (e.g. CBA/H) genotypes are highly susceptible but both can be protected against infection by injection of serum from infected mice. Using differential pH elution of "immune serum" from protein A-Sepharose, evidence was obtained that a combination of the pH 6 eluate (enriched for IgG1 molecules) plus the pH 3 or 4 eluate (enriched for IgG2 molecules) was more effective than either eluate alone at transferring protection to nude mice. By using whole serum transfer techniques, the rate of appearance of "host protective serum activity" (presumably antibody) was shown to be increased in genetically resistant versus susceptible mouse strains. It is suggested that, in relatively resistant mouse strains, host protective antibodies prejudice the establishment (or subsequent survival) of larvae prior to the full expression of protective mechanisms in the establishing larvae. In keeping with a host-protective effect of an accelerated immune response early in infection, a high dose challenge with eggs actually resulted in lower infection levels in genetically resistant mouse strains such as BALB/c and C57B1/6. The proposed mechanism of immunologically mediated, genetically based variation in susceptibility to T. taeniaeformis should not influence the effectiveness of a model vaccine against first infection in all strains of mice.