The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/- 2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/- 12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume controlled intermittent positive pressure ventilation (IPPV) and neuromuscular blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP), systemic vascular resistance (SVR), and venous admixture (QS/QT) increased significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular resistance was significantly decreased, while MBP levels were not different from those during moderate hypercapnia. No cardiac arrhythmias were recorded with any of the ranges of PaCO2. Norepinephrine levels increased progressively with each increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2 despite an increase in MBP, while moderate and severe hypercapnia produce an augmentation of the cardiopulmonary performance and DO2.