Recently cytokines have been reported to potentiate the antiproliferative effects of chemotherapeutic agents against a variety of malignant tumors. We studied the antiproliferative effect of recombinant human interferon-alpha (rHuIFN-alpha) and CPT-11 on transplantable human colon cancer H-110 in nude mice. CPT-11 was administered to the H-110-bearing nude mice intraperitonealy every 4 days and rHuIFN-alpha was administered subcutaneously every day. The weight of the individual tumor was estimated by the tumor size. The cell cycle was analyzed by flow cytometry. The single administration of rHuIFN-alpha failed to show any antiproliferative activity. The antiproliferative effects of CPT-11 alone were observed in a dose and time dependent manner. This antiproliferative activity was markedly (p < 0.05) enhanced by combination with rHuIFN-alpha. Flow cytometric analysis revealed that treatment with rHuIFN-alpha accumulated cells in the S phase. rHuIFN-alpha can enhance the antiproliferative effects of CPT-11, probably through the accumulation of the tumor cells in the S phase.