The different mechanisms of acidosis buffering were investigated in 15 RDT patients dialyzed in cross-over with four depurative techniques: acetate dialysis (AD), bicarbonate dialysis (BD), lactate hemofiltration (LHF) and hemodiafiltration (HDF) with acetate bath and lactate reinfusion fluid. Blood pH, bicarbonate, blood gases, intraerythrocytic pH - on red cell hemolisates - anion gap, L-lactate, pyruvate, adenosinmonophosphate (ADP) and 2-3 Diphosphoglycerate (2-3 DPG) levels were evaluated. During AD the intradialytic buffering is initially achieved by the CO2 fall and later by the acetate metabolism and an important bicarbonate shift from the intra to the extracellular space. A physiological compensation is obtained during BD with bicarbonate administration and a mild ventilatory response to the pCO2 increase. In LHF the massive lactate administration, with plasma levels of 7 mmol/l, strongly alters the Central Nervous System elettroneutrality inducing a hyperventilatory response with a purely pulmonary acidosis buffering. Furthermore the lactate/pyruvate ratio rose as high as 40:1 with ADP increase and cellular energy depletion. In HDF several different mechanisms are associated: the CO2 fixation, the acetate muscular metabolism, the intra-extracellular bicarbonate shift with the pulmonary response driven by lactate Central Nervous System penetration.