Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using the monoclonal antibody TIA-1, a marker of cytotoxic T lymphocytes (CTL). Many TIA-1+, CD8+ cells are distributed in active inflammatory lesions. The number of TIA-1+ cells is related to the amount of HTLV-I proviral DNA in situ. The protein TIA-1 has been associated with the induction of apoptosis in target cells. In active inflammatory lesions, we found cells undergoing apoptosis, most of them identified as helper-inducer CD45RO T lymphocytes, which were consistent with in vivo cellular tropism of HTLV-I in patients with HAM/TSP. These findings suggest that CTL-induced apoptosis of T lymphocytes may be one of the possible mechanisms which eliminate HTLV-I-infected cells from the central nervous system. In addition, many T lymphocytes in the inflammatory lesions expressed bcl-2 oncoprotein, suggesting that infiltrated T lymphocytes may be resistant to apoptosis. Expression of bcl-2 oncoprotein may explain the longstanding inflammatory process in the central nervous system of HAM/TSP.