Studies have focused on the events that influence the development of interleukin 17 (IL-17)–producing T helper cells (T_H-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T_H-17 cell effector responses. Here we show that IL-27 receptor–deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4⁺ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T_H-17 cells induced by IL-6 and transforming growth factor-β, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T_H-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.