Conventional therapy for leukemic meningitis includes cranial irradiation and intrathecal chemotherapy administered by repeated lumbar punctures or direct intraventricular instillation via an Ommaya reservoir. Several clinical reports have indicated that high doses of cytosine arabinoside (ara-C) are effective in the treatment of acute leukemia refractory to standard induction therapy. Pharmacokinetic studies have demonstrated that high doses of ara-C given intravenously obtain sustained therapeutic drug concentrations in the cerebrospinal fluid, suggesting that this approach may be useful in the treatment of systemic disease associated with meningeal involvement. Five consecutive patients with overt meningeal leukemia were treated using only systemic chemotherapy containing high-dose ara-C. In all patients there was prompt resolution of neurologic symptoms and signs accompanied by cytologic clearing of leukemic cells from the cerebrospinal fluid.