A new peritoneal dialysate containing pyruvate anions has been tested for its effects on cell functions and compared with conventional lactate and bicarbonate based solutions. The dialysate has a final pH of 5.4 to 5.6 and is composed of 1.36 to 3.86% glucose-monohydrate, 132 mmol/liter sodium, 1.75 mmol/liter calcium, 0.75 mmol/liter magnesium, 102 mmol/liter chloride and 35 mmol/liter pyruvate. For cytotoxicity testing peritoneal macrophages and peripheral blood mononuclear cells (PBMC) were exposed to conventional lactate dialysate, pyruvate dialysate, bicarbonate dialysate and a control medium RPMI 1640 (Biochrom KG, Berlin, Germany), followed by activation with different bacterial stimuli. In addition, the study further investigated the effect of varying glucose concentration in the different dialysates ranging from 0 to 3.86% and pH changes between 5.2 and 7.4 on the cytotoxicity effect on the selected cells. Mononuclear cells exposed to pyruvate-based dialysate before stimulation with endotoxin exhibited a tumor necrosis factor (TNF)-mRNA signal comparable to those of cells exposed to RPMI. In contrast, exposure to lactate-based dialysate completely inhibited TNF-mRNA synthesis. In addition, cytokine synthesis in macrophages and PBMCs after exposure to pyruvate was less inhibited when compared to the corresponding levels measured after exposure to lactate. The chemotactic response of polymorphonuclear cells and O-2 generation in all tested cell types after exposure to pyruvate was found not to be inhibited, whereas a complete inhibition was observed after exposure to lactate. The results demonstrate that cytotoxicity effects of peritoneal dialysate on cell lines can be minimized by using a new dialysate formulation containing pyruvate anions instead of lactate.