The capacity of estrogen to induce vaginal candidosis (VC) in the absence of previous or concurrent Candida albicans infections was examined. Adult female Balb/c mice were evaluated for vaginal C. albicans burden, C. albicans-specific delayed type hypersensitivity (DTH) responses and vaginal lymphocyte population kinetics at several time-points while receiving weekly injections of 0.5 mg estrogen. Estrogen treatment resulted in the appearance of significant levels of C. albicans vaginal colonization, which persisted for a period of 4 weeks. A marked suppression of DTH responses mounted against subsequent C. albicans challenge was observed. Absolute number of vaginal T lymphocytes gradually increased by several folds especially at weeks 5-6 following the start of estrogen treatment. These results clearly indicate that estrogen, independent of other predisposing factors, is capable of perturbing the commensal relationship between the host and the fungus, which results in the induction of persistent VC.