Aim: Ocular melanoma prefers to metastasize to the liver and the liver is the sole site of metastatic disease in 80% of patients. Until now there has been no standard treatment available and these patients have a very poor prognosis (median survival 2-5 months). Isolated hepatic perfusion may be an option in patients with irresectable hepatic ocular melanoma metastases. The aim of this study was to evaluate applicability, toxicity and response in this selected group of ocular melanoma patients by treatment with isolated hypoxic hepatic perfusion with retrograde outflow with melphalan. Methods: From September 2002 until July 2006 eight consecutive patients were included in this study. IHHP was performed with inflow via the hepatic artery and retrograde outflow via the portal vein during 25 min with 1 mg/kg melphalan. The perfusion was followed by a complete wash-out procedure. Results: The median total operation time was 4 h with a median blood/fluid loss of 1100 ml. No postoperative mortality was observed. Median hospital may was 9.5 days. Toxicity was moderate: WHO grade 3 leukocytopenia in 3 patients, grade 3 hepatic toxicity in 1 patient. In 37% of patients (1/8) a partial response could be demonstrated 3 months after IHHP. Stable disease was found in 3 patients and progressive disease in 2 patients. Median time to local progression was 6 months and the median survival was 11 months. Conclusion: Melphalan-based IHHP with retrograde outflow is a safe treatment option for patients with irresectable ocular melanoma metastases. Survival benefit seems to be comparable to classical IHHP. (C) 2008 Elsevier Ltd. All rights reserved.