To determine whether stopping nitroglycerin and sodium nitroprusside (both vasodilators) infusions in hypertensive, postcardiac surgical patients requiring a high FIO2 improves PaO2 and venous admixture. Prospective, clinical trial. Intensive care unit in a university-affiliated hospital. Thirty postcardiac surgical patients who, because of high FIO2 requirements, did not meet the criteria for weaning from mechanical ventilation and who were receiving infusions of nitroglycerin and/or sodium nitroprusside to control blood pressure. PaO2, venous admixture, and oxygen transport data were determined at baseline using arterial and mixed venous blood gas samples and hemodynamic values from a pulmonary artery catheter. The nitroglycerin and sodium nitroprusside infusions were stopped, and intravenous boluses of labetalol were administered to maintain a target blood pressure. After the vasodilator infusions were stopped, the baseline measurements were repeated to redetermine PaO2, venous admixture, and oxygen transport values. Results included a mean increase in PaO2 from 79.3 +/- 15 torr (10.5 +/- 2.0 kPa) to 118.3 +/- 38 torr (15.7 +/- 5.1 kPa) and a mean decrease in venous admixture from 26.4 +/- 5.8% to 17.6 +/- 5.6% when the vasodilators were stopped. All 30 patients had an increase in PaO2 and a decrease in venous admixture. Because of the improvement in oxygenation, 28 of the 30 patients met the criteria for weaning from mechanical ventilation once nitroglycerin and sodium nitroprusside were stopped or decreased. Labetalol was well tolerated in this group of patients who had preserved ventricular function. Substituting labetalol for nitroglycerin and sodium nitroprusside improves arterial oxygenation and venous admixture in hypertensive postcardiac surgical patients who require a high FIO2. This change in therapy may allow patients to be weaned from mechanical ventilation sooner.