There is a powerful, chronically activated cytotoxic T-lymphocyte (CTL) response to the Tax protein of human T-cell leukaemia virus type I (HTLV-I) in most people infected with the virus. The CTL select variant sequences of Tax which escape immune recognition and interfere with recognition of the wild-type protein. This positive selection process is more efficient in healthy HTLV-I carriers than in patients with tropical spastic paraparesis, an inflammatory neurological disease associated with HTLV-I. The mean virus load is more than 10-fold greater in patients with this neurological disease than in healthy carriers of HTLV-I. We conclude that anti-Tax CTL play an important part in limiting the rate of replication of HTLV-I. We suggest that the outcome of infection with HTLV-I is primarily determined by the CTL response of the individual: low CTL responders to HTLV-I develop a high virus load, resulting in widespread chronic activation of T cells. The activated T cells then invade the tissues and cause bystander tissue damage, probably by releasing cytokines and other soluble substances. An efficient CTL response to HTLV-I limits the equilibrium virus load, and so reduces the chance of developing inflammatory disease.