We studied the antiproliferative effect of recombinant human interferon-α/βγ (rHuIFN-α/βγ) and CPT-11 against human colon cancer xenografts in nude mice. CPT-11 (25 mg/kg) alone exhibited significant antiproliferative effects. Although rHuIFN-α/β/γ alone did not show antiproliferative activity, it markedly enhanced the antiproliferative activity of CPT-11. rHuIFN-α/β/γ significantly increased in the population of cells in the S-phase. rHuIFN-α/β/γ progressed cell cycle in the S-phase under the existence of CPT-11, which exhibited no effect on cell cycle progression. Because CPT-11 is known to exhibit antiproliferative effect on S-phase cells, IFNs, especially rHuIFN-α and β, can enhance the antiproliferative effect of CPT-11 mediated by cell accumulation in the S-phase.