The accuracy and acceptability of saliva human immunodeficiency virus type 1 (HIV-1) antibody testing were compared with serum testing in a study of paired specimens from HIV-1-seropositive and HIV-1-seronegative Ugandan adults attending a clinic for sexually transmitted diseases. Saliva collection was performed with the Omni-sal device (Saliva Diagnostic Systems, Vancouver, Wash.), and antibody testing was performed by a rapid filter paper assay (Test-Pack; Abbott Laboratories, Abbott Park, Ill.). Relative to serum testing, the sensitivity of saliva testing was 95% (195 of 205) and the specificity was 99% (295 of 297). The sensitivity of saliva testing was higher for patients with elevated levels of beta-2 microglobulin in sera and greater numbers of HIV-1-related symptoms. Pre- and poststudy interviews indicated that saliva testing did not foster inordinate fears of saliva exposure. The development of saliva tests that are inexpensive and do not require electricity is needed.