Partial immunity to schistosomiasis mansoni has been demonstrated in mice and has recently been transferred passively with serum, but not with cells. In vitro studies using human and rodent materials have demonstrated antibody-dependent cell-mediated damage to immature schistosomes (schistosomula); the cell involved in some of these in vitro systems appears to be the neutrophil and in others the eosinophil is suspected. In the present study the effect of antileukocyte sera on partial immunity to schistosomiasis was tested in vivo using quantitative assay systems for schistosomula in the lungs and adult worms in the portal venous system. Mice infected with 10 cercariae of Schistosoma mansoni 16 and 32 wk before challenge with 500 cercariae showed reductions in the recovery of schistosomula at 4 and 6 days of approximately 40%; adult worm recovery was reduced by 60%. Treatment with antilymphocyte, antimacrophage, or antineutrophil serum had no effect on the numbers of schistosomula recovered from the lungs of immune animals, but in the mice treated with antieosinophil serum the numbers of schistosomula and adult worms recovered increased to the levels seen in normal nonimmune animals. Furthermore, sera collected from the partially immune mice and passively transferred to uninfected mice conferred a marked resistance to infection as measured by recovery of schistosomula; this was also abrogated by treatment with antieosinophil serum. These studies suggest that antibody-dependent cell-mediated immunity to schistosomiasis occurs in vivo, and also establishes a role for the eosinophil in immune systems.