In an attempt to reduce myeloproliferation, we administered recombinant alpha-2b interferon (r-alpha INF) to ten patients with myelofibrosis with myeloid metaplasia (MMM) in a hypercellular phase, as part of a phase II trial. Two patients experienced severe side effects and stopped treatment before completion of the first week. In the eight evaluable patients, r-alpha INF was given for 16 weeks at an initial dosage of 3 X 10(6) U/day, with monthly increments in the case of response failure, i.e. a decrease in WBC or platelet count of less than 25% of the initial value. Two cases responded at the starting dosage, while the effective dosage was 5 X 10(6) U/day in the others. At the end of the 16th week, Hb showed minor changes: from an initial value of 12.08 g/dl, range 8.3-17.3, to 11.6 g/dl, range 7.7-18 (P = 0.12); WBC were reduced from 54 X 10(9)/l, range 6.4-69.4, to 17.5 X 10(9)/l, range 5-39 (P = 0.09, 4/8 responses); platelets decreased from 775 X 10(9)/l, range 215-1748, to 403 X 10(9)/l, range 118-730 (P = 0.008, 8/8 responses). Minor changes in spleen size were also noted, while no significant changes in bone marrow fibrosis occurred. Influenza-like symptoms and fatigue were common side effects. In conclusion, r-alpha INF has a role as a non-leukemogenic cytoreductive agent in the therapy of MMM, especially for cases with thrombocytosis.