Mucosal immune system activation may represent a critical determinant of adverse consequences associated with bacterial vaginosis (BV), such as sexual human immunodeficiency virus transmission, upper genital tract infections, postsurgical infections, and adverse pregnancy outcomes. Concentrations of sialidase, prolidase, and anti-Gardnerella vaginalis hemolysin (Gvh) immunoglobulin A (IgA) were higher in vaginal fluids of 75 fertile women with BV, compared with concentrations in vaginal fluids of 85 healthy control subjects. Interleukin (IL)-8 levels were positively associated with anti-Gvh IgA response and inversely correlated with high levels of prolidase and sialidase in women with BV. IL-8 concentration was strongly associated with leukocyte count in both healthy and BV-positive women. The absence of leukocytes in most women with BV likely is due to lack of IL-8 induction. Parallel impairment of innate and adaptive mucosal immune factors, likely through microbial hydrolytic effects, may allow for the ascent of microorganisms to the upper genital tract and may facilitate viral infections.