A patient with liver metastases of human lymphocyte antigen (HLA) class II-negative malignant melanoma was treated with several cycles of adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells. The authors evaluated the efficacy of regional transfer of LAK cells versus systemic intravenous administration. Initially, the patient was treated according to a regional treatment protocol, consisting of perfusion of the spleen with interleukin-2 and transfer of LAK cells into the portal vein; a partial remission was observed. Because of technical problems, interleukin-2 and LAK cells were administered intravenously in a second treatment cycle. This systemic treatment course resulted only in a minor mixed response of the hepatic metastases. A third treatment course was administered with the use of intravenous interleukin-2 infusion and arterial perfusion of the liver with LAK cells. The patient had separate hepatic arteries to both lobes of the liver as an anatomic variation. Because most of the tumor mass was present in the right lobe of the liver, a third of the LAK cells were injected into the right hepatic artery and the remaining cells were administered intravenously. The lesions in the right lobe of the liver regressed, but disease progression occurred in the left lobe. A fourth treatment cycle, consisting of intravenous infusion of interleukin-2 and arterial perfusion of both lobes of the liver with LAK cells, resulted in a complete response of all hepatic lesions, which has lasted 18 months to date. Because, in this patient, tumor regression was observed only in anatomic areas of the liver, which were perfused with LAK cells, it is suggested that the regional administration of LAK cells was essential for successful treatment.