T helper 1 (Th1) and Th2 cells are the major subsets of fully differentiated CD4+ T cells in the mouse. The spectrum of cytokines characteristic of each subset determines the distinctive regulatory and effector functions mediated by each subset. We have used the murine model of Leishmania major infection to study the question of whether highly polarized populations of normal T cells are as stable in their cytokine phenotype as Th clones or whether the phenotype can be altered with regulatory cytokines. Interleukin 4 (IL-4) appears to be a key cytokine for Th2 responses as it is necessary for both the initial differentiation of Th responses to L. major and the stability of ongoing responses. Furthermore, IL-4 is capable of converting highly polarized Th1 responses to Th2 responses either in vitro or when adoptively transferred to severe combined immunodeficiency mice.