The purpose of this research was to study the changes in the molecular weight of hyaluronic acid in Wharton's jelly altered by necrotizing funisitis. Umbilical cords were collected at delivery from 20 newborns without funisitis, 6 newborns with acute funisitis, and 4 newborns with necrotizing funistis. Agarose gel electrophoresis of Wharton's jelly was performed to analyze the molecular weight of hyaluronic acid (HA). We also investigated the effects of low or high molecular weight HA on the production of interleukin-8 in human umbilical fibroblasts. In Wharton's jelly without funisitis, HA was 1150 ± 280 kD in preterm newborns, regardless of gestational week at birth, and that in full-term newborns was 1100 ± 200 kD. When acute funisitis was present, HA was 700 ± 250 kD, and when necrotizing funisitis was present, HA was 520 ± kD. The molecular weight of HA was significantly below normal in newborns with necrotizing funisitis. Low molecular weight HA was associated with increased levels of IL-8 in the supernatant of cultured human umbilical fibroblasts in a time- and dose-dependent manner. High molecular weight HA did not induce the production of IL-8 in the same cells. Low molecular weight HA has a potent inflammatory action. The conversion from high to low molecular weight HA in Wharton's jelly may be important in the pathophysiology of necrotizing funisitis.