Parasitic helminths typically induce components of immediate-type hypersensitivity, including elevated serum IgE, eosinophilia, and mucosal mast cells. These responses are T-cell-dependent and associated with rapid expulsion of parasitic worms from a sensitized host; existing experimental systems have failed to define the precise role of cytokines in these responses. We report here that anti-interleukin 4 or anti-interleukin 4 receptor antibodies block the polyclonal IgE response to a parasitic nematode, Heligmosomoides polygyrus, and abrogate protective immunity to the infection. In contrast, anti-interleukin 5 antibody prevented H. polygyrus-induced eosinophilia but did not prevent protection. These data provide evidence that a specific cytokine affects the physiology and survival of a parasitic nematode in the host.