Elevated pulmonary vascular resistances occur to a variable degree in patients with chronic congestive heart failure (CHF). These might be caused by increased levels of endogenous vasoconstrictors, defective endothelial vasodilatory mechanisms or structural vascular abnormalities. To determine the contribution of defective endothelial mediated vasodilation, we tested 10 patients with CHF due to coronary artery disease (n = 4) or dilated cardiomyopathy (n = 5), and congenital corrected transposition of the great arteries (n = 1) (median pulmonary artery pressure 36 mmHg, range of pulmonary vascular resistance 0.94-10.7 WE). Patients were in median functional class NYHA III, median left ventricular ejection fraction was 21%, median oxygen uptake at the anaerobic threshhold was 8.25 ml/kg/min. Flow was measured by a flow wire (0.018 inch) positioned in a pulmonary artery branch with a diameter of 3-8 mm determined by intravascular ultrasound before. Acetylcholine infusion was adjusted to 10(-6), 10(-5) and 10(-4) molar concentrations in the pulmonary artery branch. A dose dependent increase in flow between 64 to 140% was seen in 8 out of 10 patients. We conclude: Acetylcholine mediated vasodilation is found in patients with CHF and elevated pulmonary vascular resistances.