We summarize the results of our experience over the past 15 years using pentostatin (Nipent; SuperGen, San Ramon, CA) to treat a range of mature B- and T-cell malignancies. This includes 145 patients with postthymic T-cell malignancies in whom disease subtype was found to be the most significant predictor of response, with the best response rates seen in Sézary syndrome (62%) and T-prolymphocytic leukemia (45%). However, there are no long-term survivors among patients with this group of disorders, and strategies using pentostatin in combination with other therapies, such as CAMPATH-1H, are currently being explored. Among the mature B-cell diseases, pentostatin in both standard- and low-dose regimens is effective in advanced, relapsed/refractory B-chronic lymphocytic leukaemia, showing no cross-resistance with other purine analogs such as fludarabine. Our largest series treated with pentostatin consists of 165 patients with hairy cell leukemia. The follow-up period in this group extends to more than 10 years, with a projected event-free survival rate at 5 years of 60% and an overall survival rate of 97%.