During CAPD, the peritoneal mesothelial monolayer is directly bathed in dialysate containing 1.50%-4.25% glucose. In this study, we separated and cultured mesothelial cells from human omentulum (HMC) to test the effects of glucose on cell growth and matrix biosynthesis. [3H] thymidine incorporation was significantly inhibited in cells grown in > or = 1.00% glucose, compared with cells grown in 0.10% glucose and RPMI-1640 alone. HMC incubated in RPMI-1640 medium released trace fibronectin (FN) as measured by specific enzyme immunoassay, and FN level in supernatants was significantly increased when HMC grew in the media containing glucose more than 0.50%. Glucose induced inhibition of cell proliferation and increase of FN were time-and dose-dependent. Mannitol also achieved the same results, but its inhibitive effect on HMC proliferation is far less than that of isoosmolar glucose. These studies provide evidence for a multitude of direct effects of high concentration ambient glucose level on HMC growth and matrix biosynthesis, and raise the possibility that long-term exposure of HMC to high concentration glucose may induce disturbance in cell repair and metabolism, thus contributing to the formation of sclcerosing peritonitis in CAPD.