Of the nonphysiological compounds in glucose-rich peritoneal dialysate, we investigated the cytotoxicity and synergistic cytotoxicity of acidity and glucose degradation products (GDPs) using human peritoneal mesothelial cells (HPMC). The effect of pH on cell viability was examined by adding 1N HCl to a phosphate-buffered solution (pH > or = 5.5). We also examined the cytotoxic effects of various GDPs [glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3DG), alone or in combination] and pH (5.5 or 6.7). The cells were exposed to these solutions for 2 or 4 h. Cell viability was determined by 3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. Although the MTT viability of HPMC was not decreased by GDP or acidity alone, the combination of acidity and GDP markedly decreased MTT viability, strongly suggesting the synergistic cytotoxicity of GDP and acidity.