Adult T-cell leukemia, which is caused by human T-lymphotropic virus type-I (HTLV-I), is frequently characterized by severe hypercalcemia and lytic bone lesions. The lymphokine lymphotoxin, synthesized by T-cells, has among its activities the ability to activate osteoclasts. We, therefore, examined HTLV-I-infected T-cells for evidence of lymphotoxin expression. High levels of constitutive lymphotoxin expression were noted in all HTLV-I-infected cells, but not in uninfected T-cells or those infected by human immunodeficiency virus (HIV-1). HTLV-I-mediated lymphotoxin expression appears to be dependent on the viral tax gene, and to act at the level of RNA transcription. The effect of tax is likely indirect, operating through interaction with several cellular factors.