Strips of beef coronary branch arteries, maintained in vitro, respond to decreased PO2 in the bathing medium with relaxations which are much attenuated by pretreatment with indomethacin or aspirin. It was determined that these hypoxia-induced relaxations are sustained until strips are returned to an environment of high PO2 and that the mechanism involved does not fatigue readily with repetitive exposure to hypoxic stress (53 mm Hg). It was also established that the reduced relaxations observed in the presence of inhibitors of prostaglandin synthesis were not enlarged with time by the development of an alternate process of relaxation independent of prostaglandins. Other experiments showed that when prostaglandin intervention is blocked with inhibitors the strips maintain a given level of tone to potassium chloride under a PO2 of 53 mm Hg, and do so without significant impairment over an observation period of one hour. Similarly, complete concentration-response curves to potassium did not differ under high (515 mm Hg) or low (53 mm Hg) PO2. This confirms that hypoxia-induced relaxation in beef coronary artery strips is a specific process, apparently mediated by a prostaglandin, rather than any consequence of the failure of the energetics of contraction.