BACKGROUND. Primary leptomeningeal melanomas are rare tumors that originate in the leptomeninges and are associated with a poor prognosis and no response to radiation and chemotherapy. These tumors rarely metastasize outside the central nervous system. Recombinant interleukin-2 (rIL-2) is a cytokine that activates natural killer cells and lymphokine activated killer cells, augments their antitumor effects, and recruits and activates cytotoxic T lymphocytes. We hypothesized that rIL-2 may prolong disease free survival in a patient with primary leptomeningeal melanoma. METHODS. The patient was treated with intrathecal rIL-2 via lumbar puncture daily for 5 days, then weekly for 5 weeks. To investigate whether rIL-2 induced a favorable clinical response, the following parameters were monitored: survival, neurologic status, cerebrospinal fluid (CSF) analysis, visual fields, and magnetic resonance imaging (MRI) of the lumbosacral spine. RESULTS. The patient is still alive and disease free 15 months after receiving rIL-2, and his neurologic status remains unchanged. The CSF glucose concentration, undetectable prior to therapy, has become normal. Repeated cytologic examinations of CSF were negative for malignant cells. The visual field examinations have remained unchanged. MRI scans of the lumbosacral spine have shown the development of arachnoiditis, but no recurrence of the mass lesion. CONCLUSIONS. The tumor response in this patient, as measured by remarkable disease free survival and normalization of the CSF glucose concentration, illustrates the potential benefits of intrathecal rIL-2 in the treatment of patients with this otherwise rapidly fatal disease.