The efficacy of FAM (5-FU, ADM, MMC) chemotherapy was compared with that of FEM (5-FU, EPIR, MMC) chemotherapy, in which the EPIR dose was about 1.3 times the ADM dose, by hepatic arterial infusion. Twenty-one patients with unresectable hepatic metastasis from colorectal cancer were the subjects of this multi-institutional randomized study. The response rate in evaluable 15 patients was 0% (0/6) in FAM group and 22% (2/9) in FEM group, with a 50% survival time of 15.3 months in FAM group and 15.1 months in FEM group. The major toxicities were gastrointestinal, together with hepatic dysfunction, both of which were not serious. Total incidence of > or = grade 2 toxicities was 50% (3/6) in FAM group and 80% (8/10) in FEM group. There was no statistical difference between the two groups in response rate, 50% survival time and toxicities. The clinical results of FAM and FEM were therefore considered equal, and an expected improvement in efficacy by increasing the EPIR dose was not confirmed. However, two patients in FEM group showed an objective response not observed in FAM group; one of them showed CR and survived about 3 years. These findings seem to suggest the efficacy of FEM hepatic arterial infusion chemotherapy for treatment of unresectable hepatic metastasis from colorectal cancer.