The expression of the leukemia inhibitory factor/D factor (LIF) gene in human T-cell leukemia virus type 1 infected T-cell lines was examined. Human T-cell leukemia virus type 1 infected T-cell lines MT-1, MT-2, H89-59, H89-79, and H109 expressed LIF mRNA, but the T-cell lines MOLT-4 and TALL-1 did not. LIF mRNA expression was enhanced by interleukin 2 or 12-O-tetradecanoylphorbol-13-acetate in MT-2 cells. The biological activity of LIF was detected in culture medium enhanced by interleukin 2 in MT-2 cells. The expression of LIF mRNA was suppressed by 1 alpha,25-dihydroxyvitamin D3 and dexamethasone. These results imply that the expression of the LIF gene is involved in the development of hypercalcemia and abnormalities of the immune system observed in patients with adult T-cell leukemia.