Micro‐RNA (miR) are increasingly recognized as critical regulators of tissue‐specific patterns of gene expression. CD4⁺ T cells lacking miR‐155, for example, exhibit bias towards Th2 differentiation, indicating that the absence of individual miR could alter CD4⁺ T‐cell differentiation. We now show that miR‐155 is induced upon T‐cell activation and that it promotes Th1 differentiation when over‐expressed in activated CD4⁺ T cells. Antagonism of miR‐155 leads to induction of IFN‐γ receptor α‐chain (IFN‐γRα, and a functional miR‐155 target site is identified within the 3′ untranslated region of IFN‐γRα. These results identify IFN‐γRα as a second miR‐155 target in T cells and suggest that miR‐155 contributes to Th1 differentiation in CD4⁺ T cells by inhibiting IFN‐γ signaling.