The B7 co-stimulatory pathway is critical to T cell activation, however its role in the generation of Th2 cells in vivo remains controversial. We have studied the role of B7 co-stimulation in the development of a Th2 immune response to the nematode parasite Nippostrongylus brasiliensis. Blockade of B7 co-stimulation with murine CTLA4-Ig (mCTLA4-Ig) resulted in decreased Th2 cell development as determined by IL-4 and IL-5 cytokine production in vitro. It also resulted in lowered Th2 cell effector function in vivo, with marked reductions in IgE production. Blood eosinophilia was variably affected by mCTLA4-Ig treatment, which resulted in both slight and very severe inhibition in different experiments. However, an effective immune response was still evident as demonstrated by the further reduction of cytokine production, IgE titers, and blood eosinophilia in mice treated with a combination of mCTLA4-Ig and anti-CD4 mAb, and by the ability of mCTLA4-Ig-treated mice to expel adult worms. In addition, mCTLA4-Ig treatment did not alter the development of a memory response following secondary infection with N. brasiliensis, with the exception of IgE production. We conclude from these results that B7 co-stimulation is required in this experimental model for optimal Th2 cell development and effector function in vivo but is not necessary for protective immunity.