THE latent period of AIDS is influenced by factors which activate human immunodeficiency virus (HIV) replication in different cell types. Although monocytic cells may provide a reservoir for virus production in vivo^1–8, their regulation of HIV transcription has not been defined. We now report that HIV gene expression in the monocyte lineage is regulated by NF-kB, the same transcription factor known to stimulate the HIV enhancer in activated T cells⁹; however, control of NF-kB and HIV in monocytes differs from that observed in T cells. NF-kB-binding activity appears during the transition from promonocyte to monocyte in U937 cells induced to differentiate in vitro and is present constitutively in mature monocytes and macrophages. In a chronically infected pro-monocytic cell, Ul, differentiation is associated with HIV-1 replication as well as NF-kB binding activity. These findings suggest that NF-kB binding activity is developmentally regulated in the monocyte lineage, and that it provides one signal for HIV activation in these cells.