We studied the immunological and virological effects of interferon-α (IFN-α) therapy in nine patients with HTLV-I-associated myelopathy (HAM/TSP). After therapy, the percentages of CCR5+ cells in CD4+ cells significantly decreased in the cerebrospinal fluid as well as blood. The therapy also significantly lowered the intracellular IFN-γ+/interleukin-4+ T-cell ratio in blood. Those helper T-cell type 1 (Th1)-related responses tended to be higher and reduce more evidently following therapy in three patients who clinically improved. Also, all the three patients had one or more HTLV-I copies in five blood mononuclear cells. These results suggest that IFN-α suppresses Th1 responses in HAM/TSP and that the patients with higher Th1 immunity and proviral loads may be responders of the therapy. Larger-scale studies are needed to confirm the findings.