A histopathological and ultrastructural study was made of schistosomula and associated inflammatory reactions in the lungs of normal mice, and mice previously vaccinated with irradiated cercariae. In normal mice at day 7 post-infection all schistosomula were located in blood vessels. From day 11 onwards an increasing proportion of schistosomula were intra-alveolar (80% from day 20). No cellular reactions were evident around intravascular parasites in normal mice but at later sampling times large compact foci were associated with alveolar parasites. Initial reactions, probably in response to non-specific tissue damage, were approximately 50% polymorphonuclear, and 50% mononuclear. Mononuclear cells predominated at later times. In spite of inflammation, no damage to the schistosomula was observed. There was no evidence for re-entry of schistosomula into blood vessels, and it was assumed entry into alveoli occurred accidentally as parasites attempted to traverse pulmonary blood vessels. The pattern of localization of schistosomula in vaccinated mice was similar to that in normal mice, the proportion in alveoli increasing with time (64% from day 20). The most significant difference was that intravascular schistosomula attracted foci of host leucocytes which were always 85% or more mononuclear, containing both lymphocytes and macrophages. The infiltrating cells enlarged the intersititium, separating the vascular endothelium from the alveolar epithelium. Fibrous protein was also deposited in the interstitial region. In some instances the complete blood-air barrier was destroyed by the infiltrates. Unusual paracrystalline inclusions were observed in alveolar macrophages and giant cells. The differences in cellular responses in vaccinated and normal mice suggest that challenge schistosomula stimulated an anamnestic immune response. The resulting inflammation, by impeding movement through the vasculature, terminated migration in the lungs, and accounted for the observed resistance to reinfection. The reactions in vaccinated mice have many of the features of a delayed hypersensitivity response implying that lung phase resistance in vaccinated mice may be T-cell rather than antibody-mediated.