Gonococcal and chlamydial infections in the pharynx can occur as a consequence of oral sex. Currently, diagnosis of these infections typically requires a swab specimen to be collected from the posterior pharynx. However, we assessed the diagnostic adequacy of using commercial mouthwash or water as an oral-throat rinse and subsequent testing with a nucleic acid amplification test (Gen-Probe APTIMA Combo 2 assay; Gen-Probe, San Diego, CA). Mouthwash and water samples, spiked with varying amounts of gonorrhea and chlamydia, remained positive for both organisms for up to 2 weeks after storage at room temperature and 37 degrees C. A clinical trial compared the test performance of oral-throat rinses to pharyngeal swabs among 561 (250 mouthwash, 311 water) gay and other men who have sex with men. Participants were also surveyed to assess the acceptability, preference, and feasibility of oral-throat rinses in a clinical setting. The prevalence of pharyngeal gonorrhea and chlamydia were 9.5% (53/556) and 1.4% (8/561), respectively. Compared with the pharyngeal swab, mouthwash oral-throat rinses had a sensitivity and specificity for the detection of gonorrhea of 72% and 99.1%, respectively, whereas water had 82% and 99.7%, respectively. Chlamydia prevalence was too low for reliable assessments of test performance. Study participants found oral-throat rinses acceptable, preferable, and feasible when compared with pharyngeal swabs. Further study is needed to investigate discordant results and improve the sensitivity of oral-throat rinses.