Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down-regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.