From 1979 to 1997, 146 patients had hepatectomy for metastases of colorectal cancer (curative B: 122; curative C: 24). We categorized the severity of liver metastases as follows, H1: one lobe; H2: bilateral but less than five, and H3: bilateral with five or more lesions. In H1 and H2 patients, we compared the survival rate after resection alone (including repeat hepatectomy) with that after combination therapy (resection and prophylactic arterial chemoinfusion of 12-24 g of 5-FU). In H1 patients, the 3-year survival rate of the resected group (n = 74) and combination group (n = 6) was 47.2 and 53.3, respectively. In H2 patients, the resected group (n = 16) and combination group (n = 7) had survival rates of 34.5 and 100%, respectively. In H1 cases, the 3-year recurrence rate in the remnant liver was 63.4 versus 16.7% and in H2 cases it was 58.0 versus 0%. H3 patients received one week of continuous prophylactic arterial chemoinfusion [total dose of 5-FU = 6 g]. All four patients in the H3 combination group are alive at 20, 13, 13, and 12 months after resection, while the median survival of the resection only group (n = 4) was 12.5 months. We suggest that our combination therapy may be applicable to all patients with liver metastases of colorectal cancer.