The T H 17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the T H 17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional T H 17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene–deficient mice, IL-17F–neutralizing antibodies, and adoptive transfer experiments into Rag1−/− mice demonstrated that CD4+ T cell–derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F–deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F–deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F–deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti–IL-17 cytokine therapies in T H 17-mediated human autoimmune diseases.