Uridine 5'-triphosphate (UTP) induced long-lasting contractions of isolated human brain arteries; contractions without decrement were observed for periods of up to 20-24 hours at which time the tissues were relaxed in a dose-dependent manner by theophylline. In some vessels, rhythmic oscillations accompanied the prolonged elevation in tension. In canine middle cerebral arteries, UTP produced dose related contractions within the dose range of 1.7 X 10(-6) to 1.7 X 10(-4) M; these responses were unaffected by methysergide 2.8 X 10(-7) M, phenoxybenzamine 2.9 X 10(-5) M or indomethacin 9.8 X 10(-6) M, suggesting that the UTP mechanism of action is probably independent of tryptaminergic or alpha adrenergic receptor activation, or of prostaglandin biosynthesis. The ability of UTP to produce prolonged contraction of cerebral vessels, thus, provides an in vitro preparation in which it is possible to study some of the basic mechanisms that are associated with cerebral vasospasm.