Our objective was to investigate the clinical effect of a less toxic and less acidic peritoneal dialysis (PD) fluid produced in a two-compartment bag (PD-Bio). The study had an open cross-over design in 4 stable patients, where the patient served as his/her own control. After a period of three months using conventional PD fluid the patients were switched to three months on the new PD fluid. Routine blood chemistry and transport characteristics were measured. Cell samples from overnight spent dialysis fluid were analyzed for viability, differential count, release of superoxide radicals, and cancer antigen 125 (CA 125). Subjective patient symptoms and handling properties were investigated by a patient questionnaire. Cancer antigen 125 increased significantly, and patients with discomfort or infusion pain during the control period improved during the PD-Bio period. Patient acceptance with respect to handling of the two-compartment bag was excellent and did not differ from the use of standard bags. No changes were seen in the cell samples from spent dialysate, blood chemistry, or transport characteristics between the two treatment periods. PH in the effluent dialysate was, however, significantly higher for PD-Bio at all times during the two-hour dwell. Our results suggest that a PD fluid produced to minimize the level of toxic glucose degradation products and to obtain a more physiological pH has an impact on CA 125 levels, reduces pain and discomfort in connection with infusion of fluid, and does not influence the transport characteristics.