Bacterial vaginosis is a common condition associated with increased risk of sexually transmitted diseases, including human immunodeficiency virus infections. In contrast, vulvovaginal candidiasis has a much weaker association with sexually transmitted diseases. We found that vaginal lavage fluid from women with bacterial vaginosis is deficient in antimicrobial polypeptides and antimicrobial activity compared to fluid from healthy women or women with vulvovaginal candidiasis. Effective treatment normalized the concentrations of antimicrobial polypeptides in both bacterial vaginosis and in vulvovaginal candidiasis, suggesting that the abnormalities were a result of the diseases. Unlike in vulvovaginal candidiasis, the neutrophil attractant chemokine interleukin-8 (IL-8) was not increased in bacterial vaginosis, accounting for low concentrations of neutrophil-derived defensins in vaginal fluid. In organotypic cultures of human vaginal epithelium containing dendritic cells, treatment with Lactobacillus jensenii, a typical vaginal resident, induced the synthesis of IL-8 mRNA and the epithelial human -defensin-2 mRNA, but a typical bacterial vaginosis pathogen, Gardnerella vaginalis, had no effect. When the two bacteria were combined, Gardnerella vaginalis did not interfere with the immunostimulatory effect of Lactobacillus jensenii. The loss of normal immunostimulatory flora in bacterial vaginosis is thus associated with a local deficiency of multiple innate immune factors, and this deficiency could predispose individuals to sexually transmitted diseases.The human vagina is a microbe-selective environment that supports commensal flora while resisting colonization by exogenous microbes. Lactobacilli, the predominant vaginal microbes, compete with exogenous microbes for attachment sites and nutrients and suppress exogenous flora by maintaining a low pH and secreting antimicrobial substances (bacteriocins) (2, 25). Moreover, vaginal and cervical epithelia secrete antimicrobial peptides and proteins that can contribute to the prevention of invasion by exogenous microbes (38). Despite these mechanisms, as many as 75% of women may experience an occasional vaginal infection, and some (5 to 10%) women suffer from recurrent bacterial vaginosis (BV) or vulvovaginal candidiasis (VVC) (9, 34).Epidemiologic and laboratory studies of BV indicate that this condition could alter the local host defense barrier to other infections, and, of most concern, the barrier to human immunodeficiency virus (HIV) infection. Among women in South Africa (23), sex workers in Kenya (20), and pregnant women in Malawi (35), women with BV were at two to three times greater risk of subsequently acquiring HIV than were women without BV, and this difference persisted even after adjustment for potential confounding factors. Several cross-sectional studies also reported the association of BV and HIV infection (6,12,21,30).