Fifteen patients with hairy cell leukemia (HCL) were treated with deoxycoformycin (pentostatin; dCF) (4 mg/m2 intravenous [IV] every week x 3) and recombinant interferon-alpha 2a (rIFN-alpha 2a) (3 x 10(6) units subcutaneously [SC] daily x 4 weeks) in alternating months for a total of 14 months. Eleven patients had undergone splenectomy; four had received prior systemic therapy with chlorambucil and/or steroids. All 15 are evaluable for toxicity and peripheral blood response, while 14 are assessable for bone marrow response. Toxicity was tolerable with grade 3 or 4 nausea and vomiting in three patients, neutropenic fevers in five, transient but significant depression in eight, and localized cutaneous herpes zoster in four. Circulating hairy cells were undetectable by the end of the first month in 10 of 13 patients, and by the end of the second month in the other three. Fourteen patients had bilateral bone marrow biopsies performed at baseline after 6 months of treatment, at the end of treatment (14 months), and at 6-month intervals during follow-up. Before treatment, all patients had hypercellular marrows with hairy cels replacing normal marrow elements; all showed at least a 95% clearing of their hairy cell infiltrate by 6 months of therapy. However, small collections of residual hairy cells could be detected intermittently on at least one side of bilateral samples in all patients. All patients have completed treatment with a median duration of follow-up off therapy of 27 months (range, 15 to 31 months). To date, all peripheral counts and serum soluble interleukin-2 receptor (sIL2R) levels remain stable, and no patient has had progression of the hairy cell infiltrate in the bone marrow. Although no patient achieved a pathologic complete response, alternating monthly cycles of dCF and rIFN-alpha 2a produced durable partial remissions (PRs) in all patients. Continued follow-up is required to determine the length of such remissions.