Cell-mediated natural cytotoxicity (CMNC) of fresh or long-term cultured lymphocytes collected from HTLV-positive patients or infected in vitro with the virus, was tested against K562 target cells. Severe depression of reactivity was found in fresh lymphocytes of three patients with advanced disease, in 12 in vitro established T-cell malignant lines, and two HTLV-infected cord blood (C5/MJ and C91/PL) lines. Moreover, all (eight) HTLV-1 infected cell lines listed showed a significant inhibition of CMNC of peripheral blood lymphocytes of healthy donors. Whether virus infection promotes the outgrowth of pre-existing suppressor cells and/or produce changes of the T-lymphocyte function is unknown.