SummaryAn early host defense against infection by RNA or DNA viruses is the induction, within infected cells, of tumor necrosis factor-α (TNF-α) gene transcription. The protein product of the TNF-α gene alone, or together with different types of interferons, inhibits viral propagation in diverse cell types. In this study, the effect of acute and chronic human immunodeficiency virus type 1 (HIV-1) infection on the transcription of the TNF-α and interferon-β (IFN-β) genes was examined in susceptible monocyte and T-cell lines as well as in primary human mononuclear phagocytes. Although Sendai virus, a prototypic inducer of TNF-α and IFN-β mRNA. induced the transcription of both genes in the monocyte cell lines and TNF-α in the T-cell line and in primary mononuclear phagocytes, transcription of these genes was not inducible by HIV-1. Therefore, HIV-1 was able to infect these cells without triggering the transcription of genes encoding proteins important in immediate antiviral cellular defenses. These results may explain in part how HIV-1 is able to establish persistent intracellular infections and escape acute host responses that have evolved to combat viral infection.