We have investigated the effect of TNF, a cytokine produced during most immunologic and inflammatory reactions, on HIV genome expression in human T lymphocytes. A CD4+ human T cell line (J.Jhan) was transfected with vectors permitting the expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the long terminal repeat (LTR) of HIV-1. rTNF was found to induce HIV LTR transactivation as intensely as PHA or phorbol esters. PHA enhanced TNF receptor expression in J.Jhan cells and acted synergistically with TNF on HIV LTR induction. TNF was also shown to induce well expression of a whole HIV provirus genome transfected into J.Jhan cells. The use of various CAT constructs carrying fragments of the HIV LTR, combined with bandshift assays, showed that TNF stimulates HIV transcription by acting on the kB-like enhancer element of the LTR through induction and/or activation of an NF-kB-like protein factor. Such findings are compatible with the hypothesis that TNF production participates in the pathogenesis of AIDS by enhancing HIV replication in T lymphocytes.