We examined the autologous mixed lymphocyte reaction in human T-cell lymphotropic virus type I-associated myelopathy to elucidate the known increase in spontaneous proliferation of peripheral blood lymphocytes. Proliferative responses in the autologous mixed lymphocyte reaction test were significantly increased (34,205 cpm) in cells from 9 patients with the myelopathy, as compared with findings (18,695 cpm) in the control subjects. When non-T-cell fractions were depleted from autologous mixed lymphocyte reaction cultures, proliferative responses were completely suppressed in the control subjects, while proliferation of the peripheral blood lymphocytes from the groups with the myelopathy were not affected by depletion of non-T-cell fractions. The increase in spontaneous proliferation of peripheral blood lymphocytes in patients with the myelopathy is probably not related to an increase in autologous mixed lymphocyte reactions.