Hyaluronan (HA) plays an important role in peritoneal tissue remodeling and the inflammatory process. In this study, attention was directed to the effects of various osmotic agents on HA synthesis in human peritoneal mesothelial cells (HMCs) and fibroblasts (HFBs). Following incubation with growth arrest media for 48 hours, the cells (4 x 10(4)/mL) were incubated for 72 hours in media at various concentrations (50, 100 mmol/L for crystalloid agents and 3.5%, 7% for oncotic agents) of glucose, mannitol, glycerol, sucrose, raffinose, NaCl, combined amino acids, maltodextrin, dextran 70, and hydroxyethylstarch 20. HA synthesis for 72 hours was measured by sandwich-binding protein assay. HMCs synthesized approximately 0.15 ng/cell/72 hours and HFBs 0.09 ng. All crystalloid osmotic agents significantly suppressed HA synthesis by HMCs and HFBs in a concentration-dependent manner. There was no such suppression by any oncotic osmotic agent, which, to the contrary, enhanced the synthesis by 6%-63% in HMCs. In conclusion, HMCs and HFBs may be considered sources of HA in the peritoneal dialysis effluent. Crystalloid osmotic agents suppressed HA synthesis in these cells. Oncotic osmotic agents seem to be less toxic in this regard.