Infection with the human immunodeficiency virus (HIV) causes the acquired immunodeficiency syndrome (AIDS) over a medium period of 10 years. During this time cells that actively express HIV and cells that harbor the virus in a latent form have been demonstrated in different tissues and organs of infected individuals. It is critical to delineate the cellular and/or viral factors that regulate HIV expression and latency in order to fully understand the pathogenic mechanisms of HIV disease. Among several in vitro models that have been developed since HIV has been recognized as a human pathogen, the chronically infected promonocytic cell line U1 has become one of the more broadly used surrogate models for studies of immunologic and molecular regulation of HIV expression. In particular, more than 10 different cytokines have been shown to up- or down-regulate virus production in U1 cells either alone or in synergistic combination. Autocrine/paracrine induction of HIV expression was first demonstrated in this cell line, anticipating results in more complex models of virus infection. In addition to cytokines, hormones, vitamins, and physical and chemical agents, including UV light, heat, and reactive oxygen intermediates, have been shown to reactivate quiescent integrated proviruses. Finally, U1 cells have been used as standard controls for polymerase chain reaction studies, for pharmacologic screening of potentially therapeutic agents, and as a convenient multicytokine bioassay system for studies of immunologic control of HIV expression.