With on-line formation of the substitution fluid, high substitution rates in predilution (PRD) and postdilution (POD) can be obtained (Fresenius 4008 On-Line HDF; Gambro AK 100 Ultra). The substitution fluid is branched off from the dialysate produced by the dialysate delivery system of the HDF machine. Under these conditions it is desirable to consider the effect of the different treatment modes on the acid-base status. Using Fresenius 4008 On-Line HDF machines, ESRD-patients were treated alternately with high-flux hemodialysis (HD), postdilution HDF (POD-HDF) and predilution HDF (PRD-HDF), while all other treatment parameters were kept constant, in particular the bicarbonate dialysate concentration. Plasma-HCO3, -pH and -pCO2 were measured and compared with the results of a multicompartment bicarbonate model developed by Thews. Also plasma-pO2 and K+ were measured. The results showed no significant differences between HD, POD- and PRD-HDF. Acidosis was corrected effectively and no excessive compensation of the acid-base disturbance was observed.