It has become increasingly apparent in studies of mutant mice and observations of disease that cytokine production by fully committed effector T cells within the Th1 and Th2 phenotype can vary within each group. This can potentially influence the type and effectiveness of a given immune response. The factors responsible for inducing variable Th1 and Th2 subtype responses have not been well established. Using transgenic mice expressing the myelin basic protein-specific TCR, we demonstrate here that two distinct populations of Th2 cells that are characterized primarily by differential IL-4 and IL-5 expression levels can be generated depending upon the levels of IFN-gamma present at the time of priming. We also demonstrate that populations expressing high levels of IL-4 relative to IL-5 vs those with intermediate levels of IL-4 relative to IL-5 are stable and possess distinct effector functions in an experimental autoimmune encephalomyelitis model.