The side effects of glucose degradation products (GDPs) in conventional peritoneal dialysis (PD) fluids are well described. Using the three-compartment bag concept--that is, in situ preparation of concentrated glucose solution into a standard ionic solution--a GDP-free solution can be processed. To investigate the possible impact of this product on biological and clinical parameters, we carried out a prospective cross-over study with 31 patients, comparing the short-term effects of conventional PD and GDP-free PD solutions. Classical peritoneal parameters and ultrafiltration rate did not change during the study. After three months and after six months with the three-compartment bag, cancer antigen 125 (CA125) concentration in overnight fluid increased significantly (p < 0.001) from 24.4 IU/mL to 44.4 IU/mL and 41.1 IU/mL respectively. CA125 decreased significantly (p < 0.01) to 21.7 IU/mL after three months with the conventional solution. No change in hyaluronan concentration was observed. A slight increase of procollagen III N-terminal peptide in overnight effluent with the GDP-free solution was followed by a significant reduction after three months with standard solution. In summary, our data show that the GDP-free PD fluid improves mesothelial cell mass and turnover even after a short-term period of three months. A better quality of PD solution is obtained by using the three-compartment bag.