We have previously demonstrated that pentostatin (Nipent; SuperGen, San Ramon, CA) is highly effective in the treatment of hairy cell leukemia and report here the long-term outcome of this study. Pentostatin was administered intravenously in cycles of 4 mg/m2 weekly x 3 repeated every 8 weeks. Patients who achieved a complete remission (CR) received two further cycles for consolidation. Of 28 evaluable patients, 25 achieved a CR and three a partial remission. Twenty-three patients are alive at a median follow-up duration of 118 months (range, 55 to 133 months). Of the 25 patients who achieved a CR, 14 (56%) remain in CR at a median of 119 months (range, 109 to 133 months) from the time of CR. Nine additional patients relapsed at a median time of 49 months (range, 15 to 122 months). Only three of the relapsed patients have required treatment: two patients who received cladribine achieved CRs; the third received interferon-alpha and died from hairy cell leukemia. The three patients in partial remission continue to have normal blood counts at 58, 105, and 120 months. Five patients have developed a second malignancy: one mycosis fungoides and four solid tumors. Three patients died from the second malignancies. There were no treatment-related deaths due to toxicity or opportunistic infection. Pentostatin is a highly effective agent for hairy cell leukemia and produces prolonged remissions in the majority of patients.