Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM), 5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic and immunohistochemical observations. These T cell responses were also found in asymptomatic carriers, but the responses were not as marked as those of HAM patients. IL-2 activity in the culture supernatants was much higher in HAM patients than in asymptomatic carriers; IL-2 activity correlated well with the intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2 receptors in the cell-free supernatants from HAM patients were markedly increased compared to those from asymptomatic carriers. These results indicate that spontaneous proliferation of T cells is intimately related to HTLV-I infection and is probably due to autocrine or paracrine pathways which involve IL-2 and IL-2 receptor system.