Abstract The proinflammatory activity of IL-17–producing Th17 cells has been associated with the pathogenesis of several autoimmune diseases. In this article, we provide direct evidence for a role of IL-17 in the pathogenesis of systemic lupus erythematosus (SLE). The induction of SLE by pristane in IL-17–sufficient wild-type mice did not occur in IL-17–deficient mice, which were protected from development of lupus autoantibodies and glomerulonephritis. The protection from SLE in IL-17–deficient mice was associated with a reduced frequency of CD3+CD4−CD8− double-negative T cells and an expansion of CD4+ regulatory T cells, and did not depend on Stat-1 signaling. These data affirm the key role of IL-17 in the pathogenesis of SLE and strengthen the support for IL-17 blockade in the therapy of SLE.