HIV is not usually transmitted by saliva from HIV-1-infected individuals. Antiviral substances in saliva responsible for this may include HIV-1-specific antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated saliva ADCC titers of 62 HIV-1-infected women from the Women's Interagency HIV Study (WIHS) and 55 uninfected individuals. HIV-1-infected women were less likely to have ADCC activity in saliva than in serum or cervical lavage fluid (CVL). 24% of HIV-1-positive women and a similar percentage of uninfected women had HIV-1-specific saliva ADCC activity. A significant amount of saliva ADCC activity in infected women was HIV-gp120-specific. These studies demonstrate that HIV-specific ADCC activity can be present in saliva. This activity may contribute to host defence against initial infection with HIV.