Hemodialysis-induced hypoxemia has been explained by several mechanisms: pulmonary microembolization, decreased pulmonary diffusing capacity, fall in alveolar oxygen tension, hypoventilation and ventilation/perfusion abnormalities. The objective of this study was to analyze the factors influencing pulmonary ventilation and gas exchange of 20 patients with chronic renal failure during hemodialysis performed under the following conditions: Group 1 (9 patients) dialyzed against an acetate dialysate with a cuprophan membrane; Group 2 (7 patients) dialyzed against acetate bubbled with CO2 with a cuprophan membrane; Group 3 (4 patients) similar to Group 1, but using a polyacrylonitrile membrane. Arterial and venous blood samples were obtained from the respective lines during the predialysis period (zero), at 30, 60, 120 180 and 240 min of hemodialysis, and 60 min post dialysis (300 min) for the measurement of pH, PCO2, PO2, HCO-3 and total CO2. The minute expired volume (VE), expired fractions of O2 (FEO2) and CO2 (FECO2), O2 consumption (VO2), CO2 elimination through the lungs (VCO2) and dialyzer, respiratory exchange ratio (R), dead space to tidal volume ratio (VD/VT), alveolar ventilation (VA) and alveolar-arterial O2 difference (delta AaPO2) were measured and a leukocyte count was performed for each period of hemodialysis. The patients in Groups 1 and 3 showed a significant drop in ventilation and PaO2, a slight decrease in PAO2 and a significant increase in delta AaPO2. The patients in Groups 1 and 2 showed a significant leukopenia at 30 min of hemodialysis. The volume of CO2 eliminated across the dialyzer was very similar for the three groups of patients. Group 2 did not show any drop in ventilation or PaO2. For Group 2 venous line pH was very low and PCO2 was within the normal range, in contrast to the normal or high pH and low PCO2 shown by Groups 1 and 3. This study indicates that the drop in PaO2 was partially the consequence of a slight decrease in PAO2, but mainly due to the increase in delta AaPO2. Thus the most likely cause of the decrease in PaO2 was the VA/Q imbalance brought about by a drop in ventilation. The drop in ventilation was linked not only to the volume of CO2 eliminated across the dialyzer, but also to the amount of CO2 delivered to the lungs, and to the pH and PCO2 of the venous line.