An in vitro coronary artery preparation of beef heart was found to synthesize and release continuously large amounts of a prostaglandin of the E type. Inhibition of prostaglandin synthesis with aspirin, indomethacin, or eicosa-5,8,11,14-tetraynoic acid induced a sustained contraction of the coronary artery, and pretreatment with indomethacin diminished markedly the output of prostaglandin into the bathing medium. It appears that prostaglandin E1, generated from within the vessel wall itself, may act as an intrinsic regulator of coronary artery tone in the beef heart, and that blockade of this function leads to vasospasm.