The effect of the calcium entry blockers flunarizine and nimodipine on isolated human cerebral and temporal arteries has been studied. Flunarizine induced only weak relaxation of precontracted temporal arteries in contrast to the response seen in cerebral arteries. Nimodipine invariably induced strong relaxation of both types of vessel. The effect of the calcium entry blockers on potassium (K+)-, noradrenaline (NA)- and 5-hydroxytryptamine (5-HT)-induced contraction was also examined. In general, the K(+)-induced contraction was inhibited by both calcium entry blockers, nimodipine being more potent than flunarizine, the cerebral artery being more sensitive. The response to K+ consisted of two phases; the second, slowly developing phase of contraction was more sensitive to either blocker than the initial, fast phase of contraction. Flunarizine was significantly more potent in inhibiting NA-induced contraction of the human cerebral than of the temporal artery, and there was no difference in its action on 5-HT-induced contraction of either artery. The same pattern was found for nimodipine, which was more potent in every aspect. Both calcium entry blockers induced a parallel shift in calcium-induced contraction studied by application of calcium to vessels preincubated in calcium free medium. Flunarizine was more potent on cerebral than on temporal arteries and there was no difference between the two vessels in this action of nimodipine. However, the latter was more potent than flunarizine in preventing calcium-induced contraction. The clinical implications of the two agents are discussed in relation to cerebrovascular disorders.