Although IL-4 induces expulsion of the gastrointestinal nematode parasite, Nippostrongylus brasiliensis, from immunodeficient mice, this parasite is expelled normally by IL-4-deficient mice. This apparent paradox is explained by observations that IL-4 receptor α chain (IL-4Rα)-deficient mice and Stat6-deficient mice fail to expel N. brasiliensis, and a specific antagonist for IL-13, another activator of Stat6 through IL-4Rα, prevents worm expulsion. Thus, N. brasiliensis expulsion requires signaling via IL-4Rα and Stat6, and IL-13 may be more important than IL-4 as an inducer of the Stat6 signaling that leads to worm expulsion. Additional observations made in the course of these experiments demonstrate that Stat6 signaling is not required for IL-4 enhancement of IgG1 production and actually inhibits IL-4-induction of mucosal mastocytosis.