Human T-lymphotropic virus type I (HTLV-I)--associated myelopathy (HAM) has been shown to be closely related to HTLV-I infection. However, the mechanism by which this disease occurs after infection with HTLV-I is still obscure. We found that HAM patients have unusually high proportions of CD4+ HLA-DR+ cells, CD8+HLA-DR+ cells, OKT9+ cells, and CD38(OKT10)+ cells in their peripheral blood, all of which suggest the presence of activated T-lymphocytes. Antibody titer against HTLV-I was much higher in HAM patients than in HTLV-I carriers without evident neurological disease (p less than 0.01). Polyclonal gammopathy was also observed in most HAM patients, and 6 of 10 patients were positive for rheumatoid factor. These observations, coupled with the previous observation that corticosteroid therapy improves clinical symptoms in some patients, make it likely that continuous activation of the immune system, initiated by HTLV-I infection, plays a key role in the pathogenesis of HAM.