We have examined the responsiveness of the vertebro-basilar circulation of the anesthetized Macaca nemestrina monkey to vasoactive agents infused directly into the artery. Infusion of noradrenaline caused a slight increase in vertebral arterial resistance. This constriction was less than that seen in previous experiments with either the internal or vertebral arterial resistance. This constriction was less than that seen in previous experiments with either the internal or external carotid arteries. In the presence of vasodilatation caused by inhalation of a CO2-rich gas mixture, this constriction became a dilatation. Serotonin was without significant effect on the vertebral arterial bed. Bradykinin, histamine and prostaglandin E1 all produced slight dilatation, with bradykinin being the most potent. In all cases the concentration required to produce an effect on the vasculature was much greater in the vertebral circulation than it is in the internal carotid and extracerebral circulations. We conclude that the intact vertebro-basilar circulation is much less sensitive to vasoactive agents than experiments with isolated segments of these arteries would indicate and that therefore these agents are unlikely to play a significant part in the pathogenesis of vertebro-basilar migraine.