We studied the effects of recombinant interferon alpha-2a (IFN-alpha) in 36 patients with polycythemia vera (PV) previously treated with phlebotomy and/or conventional cytostatic agents. In each patient, after at least 2 months of discontinuation of any cytotoxic therapy, the hematocrit (Hmt) was first brought to normal value by phlebotomy; IFN-alpha treatment was then begun at a starting dose of 3,000,000 IU s.c. three times a week. Response to treatment, which was assessed monthly, was defined as persistent normalization of Hmt without concomitant phlebotomy; in non-responsive patients the initial IFN-alpha weekly dosage was progressively increased. Twenty patients were responsive with a median duration of response of 7 months (range 2-25+ months); out of these, 7 patients are still under treatment and responsive at 13+, 17+, 20+, 22+, 23+, 25+, 25+ months. These findings indicate that a cohort, although small, of patients with PV (19.4%) are persistently sensitive to IFN-alpha; in this subset of patients, this cytokine can therefore provide a useful treatment option, since, contrary to conventional therapeutic approaches such as radioactive phosphorus, cytostatic agents, or phlebotomy, IFN-alpha is devoid of harmful side effects.