This study was designed to clarify the dependency of hypoxic coronary vasodilation (HCD) on the endothelium and the role of the K⁺ channels on HCD in the rabbit coronary artery. HCD was investigated in an isolated left circumflex coronary artery precontracted with prostaglandin F₂ α. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit (KH) solution. Hypoxia was induced by gassing the chamber with 95% N₂ + 5% CO₂ and was maintained for 15 approximately 25 min. Hypoxia elicited a vasodilation in the precontracted coronary artery with and without endothelium. There was no difference between the amplitude of the HCD induced by two consecutive hypoxic challenges and the effects of 20% O₂ + 5% CO₂ + 75% N₂ and 95% O₂ + 5% CO₂ control K-H solution of subsequent responses to hypoxia. Inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HCD. Blockades of the tetraethylammonium chloride-sensitive K⁺ channel abolished HCD. Apamin, a blocker of the small conductance Ca²⁺-activated K⁺ (K_Ca) channel, and iberiotoxin, a blocker of the large conductance K_Ca channel had no effect on HCD, respectively. Glibenclamide, a blocker of the ATP-sensitive K⁺ (K⁺_ATP) channel, reduced HCD. Cromakalim, an opener of the K+_ATP channel, relaxed the coronary artery precontracted with prostaglandin F₂ α. The degree of relaxation by cromakalim was similar to that by hypoxia while glibenclamide reduced both hypoxia- and cromakalim-induced vasodilatations. In conclusion, these results suggest that HCD is independent on endothelium and HCD is considered to be induced by activation of K⁺_ATP channel.