The testing of oral fluid samples for the detection of HIV antibodies offers several advantages over the testing of blood. Our objective was to evaluate a new generation of rapid and simple assays designed specifically to detect HIV-1 and HIV-2 antibodies in oral fluids (saliva). Serum and oral fluid pairs were collected from 615 high-and low-risk individuals in the United States, Peru, and the Ivory Coast. Two different oral fluid collection devices and rapid assay systems included: (1) the Orapette/SalivaCard HIV-1/ HIV-2 and (2) the Omni-Sal/ImmunoComb II HIV-1 and HIV-2. The corresponding serum pairs were analyzed by conventional ELISAs, and all reactive sera were confirmed with HIV-1 and HIV-2 Western blots. The re-sults indicated a 100% sensitivity for both rapid oral fluid assays, including successful detection of HIV-2 antibodies. Specificities ranged from 99.8% to 100%. One sample produced a reactive result by the SalivaCard while being nonreactive by the other assays including the Western blots. Both assays performed excellently, indicating that antibodies to HIV can be detected reliably in oral fluids by simple and rapid assays. This combination of rapid testing technology and the use of easily collected oral fluid samples offers an efficient and accurate alternative to conventional testing and can be appropriately applied to a variety of testing situations for the laboratory diagnosis of HIV infection.