Exchange of bodily fluids during sexual contact has been associated with the largest percentage of AIDS cases. Conditions affecting the transmission of human immunodeficiency virus across mucosal surfaces are unknown. In several viral diseases, secretory IgA plays a premier role in protection against infection, especially mucosally transmitted viruses. We propose that virus-specific secretory. IgA antibodies affect the mucosal transmission of HIV. Antibodies to HIV have been demonstrated in oral and genital secretions. No data exist on when or how secretion of these antibodies are initiated. We propose (1) that oral sexual contact or contact at another mucosal site is responsible for HIV-specific sIgA, (2) that sIgA develops partially, chronologically, independently of serum antibody, (3) that sIgA contains virus neutralizing capabilities, (4) that seronegative sexual partners of seropositive individuals have HIV-specific sIgA and (5) that oral sIgA will develop in response to HIV vaccines. In a large cohort of seronegative and serpositive male homosexuals, we will investigate the presence, titre, and time of HIV-specific secretory antibody production in salivas of these individuals. Previously collected, risk factor behavior and clinical indices will be compared to the salivary antibody data. We will assay these samples using previously established methods for detecting sIgA: Western blotting and radioimmunoprecipitation. Using saliva, secretory antibody titres will be assayed, neutralizing capability assayed and these data compared to the serum antibody data. The oral cavity may serve as a model for other mucosal site exposed to this virus. Knowledge of secretory immunity will be important in studying sexual transmission of HIV, determining transmissibility of secretions such as saliva, determining risk of HIV passage to oral health care workers, and studying possible secretory immunity to HIV vaccines.