IL‐18 was originally described as a cytokine which induced IFN‐γ production by established Th1 cells in an IL‐12‐independent manner. However, subsequent studies demonstrated that exogenous IL‐18 in the absence of IL‐12 failed to drive Th1 differentiation of naive cells and induced IFN‐γ from established Th1 cells only in combination with IL‐12. We have examined the role of endogenous IL‐18 in controlling Th1 lineage commitment. When naive TCR‐transgenic T cells were stimulated with antigen, anti‐IL‐18 antibodies resulted in partial inhibition of IFN‐γ production, but did not inhibit Th1 differentiation. To distinguish whether the inhibitory effect of anti‐IL‐18 antibodies was mediated directly by blocking IFN‐γ production or indirectly by blocking IL‐12Rβ2 up‐regulation, naive T cells from IL‐12 − / − mice were stimulated with anti‐CD3 and IL‐18. These cells failed to produce IFN‐γ, but markedly up‐regulated IL‐12Rβ2 expression. We propose that the major effect of IL‐18 on Th1 development is mediated by up‐regulation of IL‐12Rβ2 expression, thereby enhancing IL‐12‐mediated signaling. The enhancement of IL‐12Rβ2 expression by IL‐18 may be particularly important for the differentiation of foreign antigen‐ or autoantigen‐specific Th1 cells when the stimulatory concentration of IL‐12 in the microenvironment is just below the threshold required for Th1 development.