Dioxin, a prevalent environmental pollutant, is known to enhance replication of viruses in animals, but the mechanism is poorly understood. Here we report that dioxin triggers human immunodeficiency virus-1 (HIV-1) gene expression, resulting in increased production of HIV in chronically infected promonocytic U1 cells. This effect of dioxin is mediated, in part, via activation of nuclear factor kappa-B (NF-kappa B), a key cellular transcription factor that plays an important role in the induction of HIV genes and cytokine genes that regulate HIV-replication. Dioxin stimulated the production of tumor necrosis-alpha in U1 cells, and pentoxifylline, an inhibitor of TNF-alpha synthesis, inhibited dioxin induced HIV production and TNF-alpha. These studies provide a molecular and cellular basis for increased viral replication in cells exposed to dioxin.