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To find direct evidence for the sites of death of newly transformed schistosomula of Schistosoma mansoni in the skin of challenged immunized hosts, a histopathological study of the skin of chronically infected mice and of highly X-irradiated cercaria-immunized mice was made at different post-challenge times. Attrition of infecting organisms in naive mice was used as a control. In general, three main kinds of schistosomular attrition were observed: (1) in the granulocytic exudates in the epidermis, (2) in the granulocytic aggregates in the subcutaneous tissue, and (3) in the granuloma-like foci in the subcutaneous tissue. Schistosomula killed by the epidermal granulocytic exudates and by the subcutaneous granuloma-like foci occurred in all three groups of mice, but the schistosomula killed by the subcutaneous granulocytic aggregates were found only in the highly X-irradiated cercaria-immunized animals. Schistosomula killed by the epidermal granulocytic exudates were encountered occasionally in the challenged naive mice but more frequently in both the challenged chronically infected mice and the challenged highly X-irradiated cercaria-immunized mice. The number of subcutaneous granuloma-like foci was greater in the challenged mice immunized with highly X-irradiated cercariae than in the challenged naive mice or the challenged chronically infected mice. Another differentiating character among the three groups of mice was that in the highly X-irradiated cercaria-immunized group, the subcutaneous granuloma-like foci appeared on day 3 after the challenge, but on day 5 in the naive and chronically infected groups. The results clearly indicate that skin is an important site for the attrition of the challenged cercariae in the highly X-irradiated cercaria-immunized mice, and that immunity in the chronically infected and X-irradiated cercaria-immunized mice occurs by different mechanisms.