Ventilation with low tidal volumes reduces mortality in acute respiratory distress syndrome. A further reduction of tidal volumes might be beneficial, and it is known that apneic oxygenation (no tidal volumes) with arteriovenous CO(2) removal can keep acid-base balance and oxygenation normal for at least 7 h in an acute lung injury model. We hypothesized that adequate buffering might be another approach and tested whether tris-hydroxymethyl aminomethane (THAM) alone could keep pH at a physiological level during apneic oxygenation for 4 h. Six pigs were anesthetized, muscle relaxed, and normoventilated. The lungs were recruited, and apneic oxygenation as well as administration of THAM, 20 mmol/kg/h, was initiated. The experiment ended after 270 min, except one that was studied for 6 h. Two animals died before the end of the experiment. Arterial pH and arterial carbon dioxide tension (PaCO(2) ) changed from 7.5 (7.5, 7.5) to 7.3 (7.2, 7.3) kPa, P < 0.001 at 270 min, and from 4.5 (4.3, 4.7) to 25 (22, 28) kPa, P < 0.001, respectively. Base excess increased from 5 (3, 6) to 54 (51, 57) mM, P < 0.001. Cardiac output and arterial pressure were well maintained. The pig, which was studied for 6 h, had pH 7.27 and PaCO(2) 27 kPa at that time. With intensive buffering using THAM, pH can be kept in a physiologically acceptable range for 4 h during apnea.