Numerous factors contribute to host resistance to infection with Schistosoma mansoni. Although several studies have investigated the eosinophil as an effector cell of protective responses, its true role remains unclear. In vitro, human, but not mouse, eosinophils can kill schistosomula. Studies on schistosome infection susceptibility in naive or vaccinated eosinophil-deficient mice have yielded conflicting results. Using the gamma-irradiated cercariae (irr-cerc) model, we vaccinated interleukin (IL)-5 transgenic mice in parallel with background-matched controls (C3H/HeN) to examine whether innate eosinophilia contributes to increased protection from a challenge infection. In our laboratory, mean peripheral blood eosinophil (PBE) levels in IL-5 transgenic mice were 21,000 mm3, whereas in naive C3H/HeN mice this value was 240 mm3. In 3 separate experiments, both groups of vaccinated mice showed significant resistance to challenge infection. However, there was no significant difference in the percent worm reduction between transgenic IL-5 C3H mice (mean % protection = 44.3; range = 42-45%) and the control C3H/HeN mice (mean % protection = 51.7; range = 41-64%). Our findings indicate that high levels of innate PBE due to constitutive production of IL-5 do not augment irr-cerc-stimulated immunity.