Twelve patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with PCNU. All patients had prior chemotherapy and/or radiation therapy and had progressive brain metastases, documented by computerized tomography. PCNU was given as a single intravenous infusion of 90-110 mg/m2 every 6-8 weeks. There was one partial response and four patients had stable disease. Although no episodes of sepsis or bleeding occurred, seven of 17 courses led to significant granulocytopenia or thrombocytopenia. Nonhematopoietic toxicities were mild. These results indicate that systemic PCNU is unlikely to be more effective than other currently used chemotherapy in patients with malignant melanoma and CNS metastases.