Vaginal wash fluids from chimpanzees cervically infected with HIV-1 and saliva from intravenously and cervically infected chimpanzees were analyzed for total IgA, IgA1, IgA2, IgG, and albumin concentrations and for reactivity against HIV-1. No overt abnormalities were detected in salivary immunoglobulin or albumin concentrations in either group of animals. Anti-HIV IgA and IgA subclass antibodies were demonstrated in saliva from five of six intravenously infected chimpanzees and in two of four cervically infected animals, with titers ranging from 1:5 to 1:20. HIV-specific IgG antibodies could be detected in saliva from half of the systemically infected group, the highest titer being 1:2560, whereas the highest anti-HIV IgG titer in the mucosally infected group was 1:20. Western blot analyses of the first saliva samples obtained after initial virus exposure revealed IgG, IgA, and IgA subclass antibodies directed at the env, gag, or pol gene products in both groups of chimpanzees. Examination of IgG, IgA, IgA1, and IgA2 concentrations in vaginal washes from cervically infected animals showed that IgG levels were highest, but IgA and IgA subclass reactivities against HIV-1 were more prominent than that of IgG. These results demonstrate that systemic infection of chimpanzees with HIV-1 elicits mucosal responses specific for HIV, and vaginal infection of chimpanzees induces a common mucosal immune response reminiscent of that in humans.