The effects of the calcium ionophore A23187, arachidonic acid, and acetylcholine were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in physiological saline. In unstimulated rings, A23187, arachidonic acid, and acetylcholine caused endothelium-dependent contractions. The contractions of rings caused by uridine 5'-triphosphate were not affected by removal of the endothelium. An inhibitor of cyclooxygenase, indomethacin (10(-5) M), prevented excitatory responses to A23187, arachidonic acid, and acetylcholine but did not alter contractions caused by KCl. An inhibitor of thromboxane synthetase, dazoxiben (10(-4) M), significantly reduced endothelium-dependent contractions to A23187 and arachidonic acid but did not significantly affect contractions caused by acetylcholine. These results demonstrate that A23187, arachidonic acid, and acetylcholine cause excitatory endothelium-dependent responses in canine cerebral blood vessels by increasing the release of product(s) of cyclooxygenase from endothelial cells; in the case of A23187 and arachidonic acid, thromboxane A2 contributes to the endothelium-dependent contractions.