Eight strains of mice (C57BL/KsJ, SWR/J, SJL/J, BALB/cAnN, DBA/2N, A/J, B10.A(3R), and B10.A(5R) were studied in regard to the development of resistance to secondary challenge with Schistosoma mansoni following a primary infection. Also analyzed were the number of eggs recoverable from the livers of these strains after primary infection and the size of the hepatic, schistosome egg-focused granulomas newly formed at various times after infection. As previously observed by us and others, most often the degree of resistance conferred by an acute primary infection is related to the number of adult worms harbored due to the initial infection. The mean levels of protection observed in the different strains were seen to cover a spectrum from moderate to strong resistance, rather than demonstrating high or low resistance strains. There was no observable effect of the major histocompatibility complex on this resistance state. The number of eggs recoverable from the livers of the various strains was calculated on a total liver, per female worm basis, and was seen to be less in C57BL/KsJ, SWR/J and SJL/J mice. Granulomatous reactivity also varied considerably in a strain-dependent manner. These data are compared with previously reported strain differences in S. mansoni infections. Although some similarities are observed between laboratories certain strain-related discrepancies also exist and are discussed.