Patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) show increased serum levels of soluble interleukin-2 receptors (sIL-2R), a marker of T cell activation. We found that peripheral blood lymphocytes from HAM patients proliferated spontaneously and released sIL-2R when cultured in vitro. Spontaneous proliferation was observed in T cell populations (both CD4+ cells and CD8+ cells), but not in B cell-rich populations or monocyte-rich populations. There was a significant increase of IL-2 activity in the culture supernatants of peripheral blood mononuclear cells (PBMC) after 2–3 days cultivation. On the other hand, sIL-2R concentrations in the supernatants were much higher after 5 days of cultivation. Such spontaneous T lymphocytic proliferation and release of sIL-2R were also found in non-HAM HTLV-I carriers, but not as intensely as in HAM patients. HTLV-I infection causes T cell activation to release IL-2 and sIL-2R; such T cell responses may play a role in the pathogenesis of HTLV-I-associated myelopathy.