We evaluated the reliability, sensitivity, and specificity of two rapid assays, TestPack HIV-1/HIV-2 and Genie HIV-1/HIV-2, in Lagos, Nigeria. An alternative algorithm to EIA and Western blot was then examined with the TestPack HIV-1/HIV-2 used as the screening test and the Genie HIV-1/HIV-2 used as the supplemental test to differentiate HIV-1 and HIV-2 infection. In all, 845 prostitutes were evaluated for HIV-1 and HIV-2 infection using one of the two rapid tests and compared to EIA and Western blot results. Of these 845 cases, 437 samples were analyzed by both assays. Overall, 109 (12.7%) prostitutes were antibody positive for HIV-1, 13 (1.5%) for HIV-2, and six (0.7%) were dually reactive for both HIV-1 and HIV-2. Compared to Western blot, the Genie HIV-1/HIV-2 had a slightly higher sensitivity and specificity (98.4% and 99.7%) than the TestPack HIV-1/HIV-2 (97.6% and 99.3%). The alternative algorithm using both rapid assays had a sensitivity of 96.9% and a specificity of 99.9%. The Genie HIV-1/HIV-2 correctly identified 104 of 108 HIV-1 positive sera, 12 of 13 HIV-2 positive sera, and all six dually positive sera. Both assays performed well in the field. They required < 10 min to complete, no equipment, and little training. An algorithm incorporating two rapid assays can be used as a less expensive alternative to traditional testing strategies comparable in reliability to ELISA and Western blot; it provides the additional advantage of differentiating between HIV-1 and HIV-2.