GATA-3 is a transcription factor that is selectively expressed in Th2 cells and enhances Th2-specific cytokines. This study shows that the loss of GATA-3 in developing Th1 cells requires IL-12 signaling through Stat4 and is not simply due to the absence of IL-4. GATA-3 directly represses Th1 development and IFNγ production through a cell-intrinsic mechanism that is independent of IL-4 and may involve repression of IL-12 signaling. This suggests that GATA-3 expression and IL-12 signaling are mutually antagonistic, allowing for rapid dominance of one pathway during early Th development, resulting in a stable divergence in cytokine profiles. GATA-3 inhibits Th1 development by repressing IL-12 receptor expression, thereby blocking IL-12 signaling during an early developmental window. This mechanism explains the previously described extinction of IL-12Rβ2 mRNA during Th2 development. The study also shows that GATA-3 expression in Th1 cells does not inhibit IFNγ production when reintroduced after Th1 development, indicating that GATA-3's inhibitory effect is limited to the first week of primary T cell activation. The findings suggest that GATA-3 and IL-12 signaling exert mutually antagonistic effects on each other's expression, leading to the stable dominance of one pathway and the extinction of the other, generating either a Th1 or Th2 cytokine profile.GATA-3 is a transcription factor that is selectively expressed in Th2 cells and enhances Th2-specific cytokines. This study shows that the loss of GATA-3 in developing Th1 cells requires IL-12 signaling through Stat4 and is not simply due to the absence of IL-4. GATA-3 directly represses Th1 development and IFNγ production through a cell-intrinsic mechanism that is independent of IL-4 and may involve repression of IL-12 signaling. This suggests that GATA-3 expression and IL-12 signaling are mutually antagonistic, allowing for rapid dominance of one pathway during early Th development, resulting in a stable divergence in cytokine profiles. GATA-3 inhibits Th1 development by repressing IL-12 receptor expression, thereby blocking IL-12 signaling during an early developmental window. This mechanism explains the previously described extinction of IL-12Rβ2 mRNA during Th2 development. The study also shows that GATA-3 expression in Th1 cells does not inhibit IFNγ production when reintroduced after Th1 development, indicating that GATA-3's inhibitory effect is limited to the first week of primary T cell activation. The findings suggest that GATA-3 and IL-12 signaling exert mutually antagonistic effects on each other's expression, leading to the stable dominance of one pathway and the extinction of the other, generating either a Th1 or Th2 cytokine profile.