Infection with the nematode, Nippostrongylus brasiliensis, results in a Th2-dominated immune response. We describe the dynamics of this response in both local and systemic environments. Th2-type responses were evident first in the mesenteric lymph node, with parasite antigen-specific proliferation and IL-4/IL-5 release peaking at Days 7-9 postinfection, shortly before expulsion of the adult worms from the gut. IFN-gamma responses were not observed in the mesenteric lymph node. Responses in the spleen generally followed those in the mesenteric lymph nodes by 2-3 days and showed a greater degree of Th1-type cytokine production. N. brasiliensis was shown to be a powerful inducer of IL-4 responses with as few as six infective N. brasiliensis larvae eliciting IL-4 production in the mesenteric lymph node, but only high doses of larvae (600) elicited IL-4 secretion in the spleen. Similar levels of IL-4 production by lymph node cells stimulated with Con A or parasite antigen postinfection indicated the extent of polyclonal Th2 stimulation by this parasite. Infection of IL-4-deficient mice showed that despite the absence of IL-4-dependent Th2 responses, these mice were able to curtail egg production and expel adult N. brasiliensis in a time frame similar to that of fully immunocompetent animals. These results emphasize the magnitude of the Th2 response to N. brasiliensis and also show that IL-4 is not a prerequisite for the development of immunity to N. brasiliensis.