We treated 17 patients with HTLV-I-associated myelopathy (HAM) with interferon-alpha (IFN-alpha) in an open, nonrandomized, uncontrolled study. They were administered 1.5-9.0 x 10(6) international units of IFN-alpha daily for 4 weeks, and 4 patients showed a marked clinical response, 7 showed a moderate response and the others did not show any clinical response. Increased unstimulated (spontaneous) peripheral blood lymphocyte (PBL) proliferation was observed in all patients who were measured lymphocyte transformation. Spontaneous PBL proliferation was significantly inhibited by IFN-alpha treatment (P less than 0.01), whereas anti-HTLV-I-antibodies did not show any significant changes. Likewise, decreased stimulation indices to phytohemagglutinin (SI) due to increased spontaneous PBL proliferation were significantly increased after IFN-alpha treatment (P less than 0.01). In the patients who showed marked clinical responses, the changes of SI in IFN-alpha treatment were higher than those in other patients. These data indicate that further studies are warranted for evaluation of IFN-alpha treatment of HAM in a randomized, controlled study.