T helper (Th)17 cells constitute a distinct subset of CD4 þ helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)gt directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel RORgt isoform, RORgt-D(5 --8), which lacks the hinge-encoding exons 5 --8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that RORgt-D(5 --8) acts as a dominant-negative regulator of RORgt-mediated gene regulation and the balance between the full-length RORgt and the novel repressor isoform may arbitrate IL-17 production in human T cells.