Hyaluronic acid synthesis was studied in human gingival fibroblast cultures exposed to human dental bacterial plaque extract. The cells were stimulated to produce large amounts of hyaluronic acid (HA) into the culture medium. The extract did not have any direct effect on the activity of hyaluronic acid synthetase enzyme complex, indicating that the increased hyaluronic acid synthesis was caused by metabolic alterations in gingival cells. Dental plaque extract also decreased the molecular weight of hyaluronic acid. This was obviously caused by the plaque derived hyaluronidase, because denaturation of plaque proteins by heating prevented this degradation. On the other hand, the stimulatory effect on the HA synthesis by the plaque extract was not destroyed by heating. The increased production of low molecular weight HA by gingival fibroblasts after plaque exposure is suggested to have a role in the pathogenesis of chronic periodontal diseasein vivo.