IFN‐γ , a product of NK and T cells, is a key cytokine contributing innate and adaptive immunity. IFN‐γ  production is induced via direct cell‐cell contacts with APC and IFN‐γ ‐producing cells or by cytokines. During microbial infections macrophage‐derived IFN‐α , IL‐12, and IL‐18 enhance IFN‐γ  production and Th1 response. Here we show that IFN‐α  in combination with IL‐18 very efficiently induces IFN‐γ  expression also in primary, nonactivated NK cells and in NK‐92 cell line. Comparison of the kinetics of IFN‐γ  mRNA expression in nonactivated NK cells, NK‐92 cells and activated T cells stimulated with IFN‐α  or IL‐12 revealed that, although both of these cytokines directly up‐regulate IFN‐γ  mRNA expression, its levels remain elevated much longer with IL‐12 stimulation. In both NK cells and T cells, Stat4 is known to be critical in IL‐12 and IFN‐α  signaling. We show that Stat4 activation is transient in cells stimulated with IFN‐α , whereas IL‐12 induces more long‐lasting activation of the transcription factor. This prolonged activation of IFN‐γ  gene by IL‐12 may result in more efficient IFN‐γ  production compared to that of IFN‐α . Our results demonstrate that IFN‐α  and IL‐18 are important innate cytokines in inducing NK cell IFN‐γ  production.