Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrices. HA is present in high concentrations in tissues undergoing remodeling and morphogenesis, and it appears to have an important role in the early stages of wound healing. Here, we studied the level of HA in the peritoneal dialysate effluent (PDE) from 116 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Longitudinal studies over a period of 6 weeks were performed in seven of these patients who developed peritonitis. The median HA level in PDE from these patients was 154.6 microg/L (range, 29.7 to 820.2 microg/L). Dialysate level of HA increased with age of the patients, but no such correlation was shown between HA level in PDE and duration of CAPD treatment or previous episodes of peritonitis. Patients with high or average peritoneal membrane transport of small solutes had a higher HA level in the PDE than those with a low peritoneal membrane transport (P = 0.046). A significant correlation was observed between PDE level of HA and interleukin-1beta (IL-1beta) or IL-6. The plasma level of HA in these patients was significantly greater than that of healthy controls (P < 0.0001), yet the plasma concentration of HA was only 85% that of the PDE concentration. In CAPD patients with peritonitis, there was a sharp increase in the PDE levels of HA, IL-1beta, and IL-6. These values decreased progressively with resolution of peritonitis. The changes in the PDE levels of HA closely followed those of IL-1beta or IL-6. In vitro [3H]-glucosamine incorporation studies suggest that the main bulk of HA is derived from synthesis by the peritoneal mesothelial cells, whereas the amount synthesized by macrophages is trivial. We conclude that elevated levels of HA found in the PDE of stable CAPD patients originate from increased synthesis by peritoneal mesothelial cells. This event may serve as a marker of regeneration and remodeling of the peritoneal lining.