Previously, we reported that signal transducers and activators of transcription (STAT)-1 was required for optimal Th1 cell differentiation. T-bet is the master regulator and STAT1 promotes Th1 cells partly through upregulating T-bet and interferon γ(IFN-γ). However, the mechanism that leads to silence of interleukin (IL)-4 expression in Th1 cells has not been fully understood. In this study, we further dissected signaling pathways that contribute to repression of IL-4-producing potential in Th1 cells. We showed that blockage of IFN-γ signaling resulted in failure to suppress IL-4-producing potential. Consistently, IFN-γ efficiently antagonized IL-4 signaling while IL-12 failed to do so, suggesting that IL-12/STAT4 signaling might not be required for IFN-γ-mediated function. To support this, we discovered that IFN-γ signaling inhibited IL-4-producing potential in STAT4-deficient CD4+ T cells. On the other hand, T-bet deficiency abrogated IFN-γ-mediated suppression of IL-4-producing potential. These observations suggest that T-bet but not STAT4 is required for IFN-γ-mediated suppression of IL-4-producing potential.