Although the mechanisms regulating the cerebral microcirculation during neural activity have been the subject of inquiry for a century or more, the mediators responsible for the changes in cerebral blood flow still remain to be clearly identified. The discovery that nitric oxide, a powerful cerebrovasodilator, is produced by active neurons has led to the hypothesis that this agent could be the long-sought mediator 'coupling' brain activity to cerebral blood flow. This hypothesis is supported by recent experimental data suggesting that nitric oxide participates in the maintenance of resting cerebral blood flow and in the cerebrovasodilatation elicited by increased neural activity. In this article, this evidence is critically reviewed and discussed in the context of general principles of cerebrovascular regulation.