Interleukin (IL)‐23 is a heterodimeric cytokine consisting of a novel p19 molecule and the p40 subunit of IL‐12. Since secreted p40 can act as an antagonist for IL‐12, we investigated whether p40 also inhibited IL‐23‐mediated immunological functions. p40 did not induce interferon (IFN)‐γ or IL‐17 production from splenocytes but impaired IL‐23‐induced cytokine production by competitive binding to the IL‐23 receptors. Furthermore, a mixed population of murine colon carcinoma Colon 26 cells transduced with the p40 gene and those transduced with the IL‐23 gene developed tumours in syngenic mice, whereas the IL‐23‐expressing Colon 26 cells were completely rejected. p40 also suppressed IFN‐γ production of antigen‐stimulated splenocytes and IL‐23‐mediated cytotoxic T‐lymphocyte activities in the mice that rejected Colon 26 cells expressing IL‐23. p40 can thereby antagonize IL‐23 and is a possible therapeutic agent for suppression of IL‐23 functions.