Ketamine has been used in patients with congenital heart disease and pulmonary hypertension with hypothetical controversy. Its direct effect on pulmonary arteries has not yet been clearly characterized. This in vitro study was performed to determine the direct vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Responses of pulmonary artery rings from New Zealand white rabbits were assessed in the presence and absence of intact endothelium and with or without precontraction by norepinephrine (NE, 3x 10−6M) or potassium chloride (KCl, 3x10−2M). Using a preparatory tissue bath, cumulative concentration response curves of ketamine were obtained at different concentrations (0.03, 0.1, 0.3, 1, 3 mM) after a period of stabilization. Ketamine caused a dose-related vasodilation on KCl-precontracted pulmonary arteries. It elicited almost 100% relaxation at a concentration of 3 mM. Ketamine also induced a dose-related vasodilation on NE-precontracted pulmonary arteries at a lesser degree. All of the effects were endothelium independent. In conclusion, ketamine has strong endothelium-independent, direct vasodilatory effects on isolated rabbit pulmonary arteries. Ketamine may act through Ca++ channel-blocking effect as well as inhibition of Ca++ release from sarcoplasmic reticulum.