These studies demonstrate that HIV-1 REV and HTLV-1 REX are site specific RNA binding proteins. In addition, the REV protein studies indicate a protein domain essential for biological function that is not involved in RRE binding. Lentiviruses are unique among retroviruses in providing gene products to switch expression from early to late genes. Rather than transcriptional control, this is accomplished by regulating RNA transport. A further understanding of these lentiviral genes may identify means of inhibiting viruses responsible for insidious human disease.