The liver is an large immunologic organ with liver-associated macrophages (Kupffer cells) and natural killer-like primitive T cells. As these effectors are activated by interleukin-2 (IL-2), we have administered IL-2-based hepatic arterial infusion therapy in the treatment of patients with liver metastases of colorectal cancer. Patients with unresectable liver metastases were administered IL-2 7 x 10(5) U and 5-fluorouracil (5-FU) 250 mg/day as a continuous infusion, with a bolus injection of mitomycin C (MMC) 4 mg once weekly. Of 25 patients treated with this regimen, 19 achieved complete or partial responses (response rate: 76%). A multi-institutional randomized trial following the pilot study showed reproducible favorable results. For patients with resectable metastases, we have administered this infusion therapy for the prevention of cancer recurrence in the liver. Patients who had undergone curative hepatectomy received IL-2 1.4 to 2.1 x 10(6) U, 5-FU 250 mg and MMC 2 to 4 mg weekly for 6 months. Of 18 patients, 12 are alive disease-free, and the 5-year overall survival rate is 75%. Recurrent cancer has developed in 6 of the 18 patients; however, no patients had recurrence in the residual liver. We believe that liver metastases of colorectal can be controlled by this multimodal treatment.