Immunity to Onchocerca microfilariae (mf) in mice is associated with CD4+ Th2 cells and is dependent on IL-5. In view of the role of IL-4 in the development of Th2 cells, we have utilized IL-4 gene knockout mice (IL-4-/-) to investigate microfilarial clearance and resistance to reinfection. Paradoxically, in the absence of IL-4 there is accelerated clearance of microfilariae during a primary infection and unimpeded expression of resistance to reinfection. IL-4-/- mice showed a lack of an IgE response although peripheral eosinophilia was equivalent to wildtype controls. The data presented here suggest that elimination of mf can occur independent of IL-4 and that in this model it may even be detrimental to the host.