The art/trs transactivator protein of human immunodeficiency virus (HIV) was expressed in mammalian cells as a 19-kilodalton protein that was immunoreactive with sera from HIV-infected patients. Separate plasmids encoding the art/trs protein, the tat protein, or the envelope glycoprotein gp120 were used to demonstrate that both art/trs and tat are absolutely required for the synthesis of gp120 from its cognate messenger RNA. In addition, both the tat and art/trs proteins influence the level of envelope RNA. The results suggest that art/trs and tat may be ideal targets for potential anti-HIV agents in AIDS therapy.