Experimental autoimmune encephalomyelitis (EAE) is mediated by Th1 and Th17 cells. Invariant NKT (iNKT) cells prevent EAE in an IL-4–, IL-10–, and IFN-γ–dependent manner. However, which of the iNKT cell-produced cytokines regulates the Th1 or Th17 response in EAE remains unclear. Wild-type B6 and Jα18−/− mice were immunized with MOG 35–55 peptide to address this issue. Clinical scores for EAE, IL-17, and IFN-γ transcript levels, and IL-17–or IFN-γ–expressing CD4+ T cell percentages in the CNS and draining lymph nodes were higher in Jα18−/− than in B6 mice, but all of these parameters in the CNS were reduced by the adoptive transfer of wild-type or IFN-γ–deficient iNKT cells into the Jα18−/− mice before immunization. In contrast, adoptive transfer of IL-4–or IL-10–deficient iNKT cells into Jα18−/− mice decreased IL-17 transcript levels and the percentage of IL-17–expressing CD4+ T cells in the CNS but did not affect clinical scores, IFN-γ transcript levels, or the percentage of IFN-γ–expressing CD4+ T cells in the CNS. Taken together, IL-4–and IL-10–producing iNKT cells inhibit the Th1 cell response, but not the Th17 cell response, although wild-type iNKT cells suppress both the Th1 and Th17 responses in the CNS during EAE. Moreover, IFN-γ–producing iNKT cells have a minimal role in the regulation of the Th1 and Th17 responses in EAE.