Bacterial vaginosis, Prevotella species, and Bacteroides species have been associated with prematurity and upper genital tract infection. Prevotella (Bacteroides) species and Bacteroides fragilis have also been associated with preterm birth. However, the mechanism by which lower genital tract infection causes upper genital tract disease remains poorly understood. Sialidases (neuraminidases) are enzymes which enhance the ability of microorganisms to invade and destroy tissue. Elevated levels of sialidase activity were detected in 42 (84%) of 50 vaginal fluid specimens from women with bacterial vaginosis and none of 19 vaginal fluids from women without bacterial vaginosis (P less than 0.001). Vaginal fluid from women with bacterial vaginosis had a median specific activity of 9.8 U compared to 2.5 U of sialidase in women without bacterial vaginosis (P less than 0.001). In order to determine the probable source of sialidases in vaginal fluid, the microorganisms recovered from women with bacterial vaginosis before and after treatment were assayed. Of 28 specimens from women with bacterial vaginosis, 27 (96%) yielded sialidase-positive bacteria, at a median concentration of 10(6.5) CFU/ml of vaginal fluid. Prevotella and Bacteroides species accounted for the sialidase activity in 26 of the vaginal fluids, and Gardnerella vaginalis accounted for the sialidase activity in the remaining fluid. After treatment, sialidase was detected in the vaginal fluid of 1 (5%) of 22 women who responded to therapy and in all of 6 women for whom therapy failed. These data suggest that vaginal fluid sialidase is highly correlated with bacterial vaginosis and that the probable sources for this enzyme activity are the Bacteroides and Prevotella species present in the vagina.