Vulvovaginal candidiasis (VVC) caused by Candida albicans is a significant problem in women of childbearing age. Unfortunately, protective host defense mechanisms against VVC are poorly understood. Although rodent models of experimental vaginal candidiasis have been useful, several differences from humans limit the correlation of experimental data. The purpose of the present study was to examine two species of macaques as an alternative model of experimental vaginitis. Screening of pig-tailed and rhesus macaques demonstrated that each had mucosal Candida colonization and prior immune sensitization to C. albicans. Vaginal-associated immunity (cytokines, antibodies, and innate resistance) was also detected in cervicovaginal lavage fluid from both species. Nevertheless, intravaginal inoculation of C. albicans into both species, either untreated or under estrogen-treated conditions, resulted in vaginal infection in rhesus, but not pig-tailed, macaques. Several estrogen-dependent changes in the rhesus immune status coincided with susceptibility to infection. Taken together, these results suggest that pig-tailed and rhesus macaques may be useful in studying pathogenesis and immunity associated with C. albicans vaginitis.