STAT3 activation has been observed in several autoimmune diseases, suggesting that STAT3-mediated pathways promote pathologic immune responses. We provide in vivo evidence that the fundamental role of STAT3 signaling in autoimmunity relates to its absolute requirement for generating T H 17 T cell responses. We show that STAT3 is a master regulator of this pathogenic T cell subtype, acting at multiple levels in vivo, including T H 17 T cell differentiation and cytokine production, as well as induction of RORγt and the IL-23R. Neither naturally occurring T H 17 cells nor T H 17-dependent autoimmunity occurs when STAT3 is ablated in CD4 cells. Furthermore, ablation of STAT3 signaling in CD4 cells results in increased T H 1 responses, indicating that STAT3 signaling skews T H responses away from the T H 1 pathway and toward the T H 17 pathway. Thus, STAT3 is a candidate target for T H 17-dependent autoimmune disease immunotherapy that could selectively inhibit pathogenic immune pathways.