Extracorporeal techniques for respiratory support in the newborn are feasible, as the growth of neonatal extracorporeal membrane oxygenation (ECMO) has demonstrated. It has been shown, however, that even in severely damaged lungs, sufficient oxygenation and gas exchange can be maintained only by removing CO2 in an extracorporeal circuit, i.e., extracorporeal CO2 removal (ECCO2R). To demonstrate the effectiveness of CO2 removal in a bicarbonate-free hemodialysis procedure, CO2 removal was measured during routine acetate hemodialysis in 22 patients on renal replacement therapy for end-stage renal disease. By comparison of predialyzer and postdialyzer total CO2, an overall CO2 removal of 79.1 +/- 15.1 ml/min was measured in the blood and 77.0 +/- 19.5 ml/min in the dialysate; this was approximately one third of the entire metabolic CO2 production and probably accounted for the secondary hypoxia during acetate hemodialysis. To use bicarbonate-free hemodialysis for total metabolic CO2 removal, acetate dialysate was modified with lactate, phosphate buffer, and sodium hydroxide to compensate for the bicarbonate loss. In sheep, apneic oxygenation could be achieved with blood flow rates as low as 10-15 ml/kg/min for 4-6 hours. These preliminary data suggest that a hemodialysis procedure for bicarbonate and CO2 elimination (ECBicCO2R) could be an efficient method for CO2 removal requiring much lower blood flow rates than techniques presently in use.