Glibenclamide is a sulfonylurea used in the management of diabetes mellitus but which is also known to have antagonist activity against the effects of some eicosanoids on smooth muscle. We have examined the action of glibenclamide against contractions of rings of canine middle cerebral artery by prostaglandins F<sub>2α</sub>, E<sub>2</sub> and D<sub>2</sub> and the thromboxane A<sub>2</sub> analog U46619. All these responses were significantly attenuated by glibenclamide, while contractions to potassium chloride, noradrenaline, 5-hydroxytryptamine or caffeine were unaffected. The effects of glibenclamide against the vascular actions of oxyhemoglobin were also examined, since this agent is believed to be responsible for the vasospasm which follows subarachnoid hemorrhage. Contractions to oxyhemoglobin were significantly inhibited by glibenclamide, which suggests that at least part of the contractile effects of oxyhemoglobin in cerebral arteries is mediated by eicosanoids. Glibenclamide is thus an agent which selectively blocks the contractile effects of both eicosanoids and oxyhemoglobin.