An oral fluid-based test for antibodies to human immunodeficiency virus (HIV), equivalent to serum in its accuracy but safer and easier to use, is now available in the United States. The development of the oral test involved overcoming technical obstacles to the use of oral fluid as a testing medium, including low immunoglobulin G (IgG) titers, suboptimal assay performance, protease degradation of IgG, high viscosity, and lack of a standardized method of specimen collection, all of which contribute to suboptimal assay performance. The currently available oral HIV test utilizes a collection device to isolate a mucosal transudate component of oral fluid rich in IgG. A vial containing a preservative solution facilitates the transport of stable, low-viscosity specimens to the laboratory for testing with an ELISA and confirmatory Western blot assay, specifically designed for use with oral fluid. Non-HIV medical conditions and oral pathologies do not appear to affect oral test results. Hopefully, the availability of a more patient-friendly, portable diagnostic test for antibodies to HIV will facilitate identification of greater numbers of infected individuals with the ultimate goals of early identification, early treatment, and prevention of disease transmission.