Hepatic arterial infusion (HAI) with pharmacokinetic modulating chemotherapy (PMC) has been well known to be one of the most effective protocols for unresectable liver metastases from colorectal cancer. PMC is a combination of oral UFT and continuous hepatic arterial 5-FU infusion. We present herein the cases of two patients with multiple liver metastases from colorectal cancer in whom complete regression (CR) was achieved by HAI with PMC in combination with Lentinan (immunostimulator). These patients received HAI via an implantable port system with a 4-24-hour continuous perfusion of 5-FU at 1,000 mg/m2 plus Lentinan at 2 mg/body once a week, and oral administration of UFT at 200-300 mg/m2/day everyday. CR of all metastatic lesions in the liver was achieved 4 months after the initiation of the treatment in both patients. One patient maintained CR for 3 months, but he died due to a recurrence of liver metastases and peritoneal dissemination 19 months after the initiation of the treatment. The other patient has been well without recurrence for 21 months. Because the liver is the largest immunologic organ, Lentinan could have activated lymphocytes and macrophages in the liver. Judging from the clinical experience of these two cases, HAI with PMC in combination with Lentinan could be one of the most promising treatment strategies for unresectable liver metastases from colorectal cancer.