Sensitized or chronically infected CBA/J mice were challenged percutaneously with cercariae of Schistosoma mansoni. Early inflammatory response was characterized by edema and neutrophil infiltration directed toward penetration tracks; chief pathology associated with schistosomula was localized disruption of epithelial cell relationships, except in areas of desmosomes. By 24 hours eosinophils were the prominent cells in the inflammatory reaction, with large numbers replacing neutrophils in penetration tracks. Extensive local eosinophilia occurred in areas of widespread epidermal destruction and collagen damage. Electron microscopy revealed degranulation of eosinophils in microabscesses and in areas of collagen damage and metabolically active fibroblasts. Eosinophils were rarely observed in contact with schistosomula. No marked difference could be observed between sensitized (but unprotected) mice and chronically infected mice in their response to cercarial challenge; a similar eosinophil response took place whether the mice were partially protected or totally unprotected. The data indicate that although eosinophils may be involved in this protection their presence alone is not sufficient to afford acquired resistance to murine schistosomiasis mansoni.