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postoperative recurrence of human hepatocellular carcinoma (hcc) is the major issue that must be addressed to further improve prognosis. this study was undertaken to investigate the effects of interferon-alfa-1b (ifn-a-1b) on recurrent tumor and metastasis after curative resection in nude mice bearing an hcc xenograft with high metastatic potential. tumor tissues from lci-d20, a metastatic model of hcc in nude mice, were orthotopically implanted in 105 nude mice. eleven days later, 64 mice underwent curative resection of liver tumors. ifn-a at different doses was administered subcutaneously to mice with or without resection. in mice without resection, when comparison was made among control, ifn 7.5 3 106 u/kg/day, 1.5 3 107 u/kg/day for treated groups, and 3 3 107 u/kg/day; tumor volume was 8,475 mm3 6 2,636 mm3, 7,963 mm3 6 3,214 mm3, 769 mm3 6 287 mm3, and 13 mm3 6 9 mm3; incidence of lung metastasis being 100%, 80%, 40%, and 0%; life span was 45 6 4 days, 53 6 8 days, 81 6 6 days, and 105 6 24 days, respectively. in mice with curative resection, when comparison was made among control, ifn 5 3 105 u/kg/day, 1 3 106 u/kg/day, 4 3 106 u/kg/day, 7.5 3 106 u/kg/day, 1.5 3 107 u/kg/day, and 3 3 107 u/kg/day for treated groups; incidence of recurrent tumor was 100%, 100%, 87.5%, 100%, 87.5%, 62.5%, and 12.5%; lung metastasis being 100%, 75%, 87.5%, 50%, 62.5%, 0%, and 0%, respectively. ifn-a inhibited neovascularization induced by lci-d20 tumor specimens implanted into the micropocket of nude mice corneas. in conclusion, high-dose and longterm therapy with ifn-a dose-dependently inhibits tumor growth and recurrence after resection of hcc. the effect of ifn-a may be attributed to antiangiogenesis in this experiment. these results provide potential clinical implication, particularly for the prevention of recurrence after curative resection of hcc.