Hypoxic vasoconstriction has been the subject of many studies, but little is known about the interaction of hypercapnia and the pulmonary circulation. We performed two haemodynamic studies on each of three patients with pulmonary vascular disease secondary to congenital heart disease. On the first occasion ventilation was inadequate due to technical problems, and the patients were therefore hypercapnic (arterial pCO2 greater than 5.3 kPa). On the second occasion, they were normocapnic. Pulmonary vascular resistance was measured on each occasion while the patients were breathing 100% oxygen (alveolar hyperoxia) and while epoprostenol (prostacyclin) was infused at doses of 5-20 ng/kg/min. Pulmonary vascular resistance was elevated in the presence of hypercapnia and, despite oxygen and epoprostenol, could not be reduced to the levels observed in the normocapnic study. We conclude that hypercapnia causes significant vasoconstriction in infants; and that epoprostenol is a relatively ineffective pulmonary vasodilator in infants who are hypercapnic due to inadequate ventilation. Where possible, respiratory acidosis should be corrected before using oxygen or epoprostenol as a pulmonary vasodilator.