The effects of endogenous hyaluronan on cervical ripening during pregnancy were examined in rabbits. Hyaluronan of approximately 620 kilodalton (kDa) was detected in the uterine cervix on the 25th and 29th days of pregnancy, while it was not detected in cervix of non-pregnant animals. In addition, low-molecular-weight (less than 191 kDa) hyaluronan was present in cervix at the 29th day of pregnancy. Hyaluronan level in the cervix was lower on the 29th day than on the 25th day of pregnancy, whereas that in serum was significantly higher on the 29th day than on the 25th day of pregnancy. To clarify the physiological functions of endogenous hyaluronan, the effects of hyaluronan (HA600-700), which had approximately equal to endogenous hyaluronan, on uterine cervical tissues and uterine cervical fibroblasts were examined. Rabbits at the 23rd day of pregnancy were administered a vaginal suppository of HA600-700 (20 mg) daily for three days. Promotion of cervical ripening was observed, as well as detachment of collagen fiber bundles, and a reduced density of collagen fiber distribution. Total collagenolytic activity was increased significantly by HA600-700 (1.0 mg/ml) treatment in cultured uterine cervical explants of pregnant rabbits as compared with the untreated group. Moreover, very similar effects of HA600-700 treatment (0.1, 1.0 mg/ml) were observed in cultured uterine cervical fibroblasts. Further, in tissue cultures, but not cell cultures, of pregnant rabbit cervix, prostaglandin E2 (PGE2) production was enhanced by HA600-700 treatment. Therefore, it appears that endogenous hyaluronan is closely concerned with cervical ripening and dilatation in uterine cervix of pregnant rabbits.