We administered alpha-interferon (alpha-IFN) and gamma-globulin (gamma-gl) to patients with HTLV-I-associated myelopathy (HAM). Patients selected for this study fulfilled the diagnostic criteria of HAM by Osame et al. As for alpha-IFN, 12 patients were injected intramuscularly with a dose of 3 X 10(6) IU/day of alpha-IFN for 28 days. As for gamma-gl, 10 patients were injected intravenously with a dose of 10 g/day of human gamma-gl for 5 days. alpha-IFN exerted therapeutic effects in 7 of 12 patients and gamma-gl in 6 of 10. The therapeutic effects were shown by the improvement in time for a 20-meter walk, muscle power of lower limbs and urinary frequency. All patients having a history of improvement by corticosteroid therapy showed beneficial responses to both treatments with alpha-IFN and gamma-gl. Contrarily, patients who had not improved by corticosteroid therapy did not show any improvement after gamma-gl and alpha-IFN administration. The therapeutic effects of gamma-gl and alpha-IFN were observed predominantly in cases with shorter duration of illness, more marked abnormality in cerebral MRI findings and higher CSF antibody titers to HTLV-I. There was no correlation between the therapeutic efficacy and clinical severity or serum antibody titers to HTLV-I. We conclude that therapies with alpha-IFN and gamma-gl were safe and effective for the treatment of HAM.