In order to examine the relationship between host leukocytic reactions to schistosomula and innate or acquired resistance to Schistosoma mansoni, in vivo pulmonary cell responses in CD/F rats, LVG hamsters, C57BL/6 and CBA mice, following either cercarial skin exposure or intravenous injection of schistosomula (the “lung model”), were quantified and analyzed. Major leukocytic reactions to schistosomula injected into the lungs varied according to host strain, with increasing responses occurring in the order CBA<LVG<C57<CDF. Adult worm recoveries, by portal perfusion of these hosts, ranked in a strain order reciprocal to that of lung cell responses. All hosts developed anamnestic, eosinophil-enriched responses on secondary intravenous schistosomula challenge. In mice, this in vivo eosinophilic, augmented response could be elicited by glutaraldehyde-fixed as well as by intact challenge schistosomula. After primary percutaneous cercarial exposure, lung responses at 5 days were significant in rats, and after secondary challenge, in both rats and hamsters, but were virtually nil in mice, whether previously exposed to S. mansoni or not. Thus, schistosomulum attrition was partly dependent on parasite encounters of various kinds with host mono- and granulocytes, but was of major consequence only in hosts with native (rat) or acquired resistance (all hosts), while playing a minor role in naive permissive hosts (mouse, hamster). The failure of previously-infected mice to develop early lung residual killing foci in response to skin-penetrated schistosomula is unique among the known laboratory hosts of S. mansoni.