Abstract NONOates are a new class of NO donors that have proven useful for studying the effects of spontaneous and chemically predictable NO release in biologic systems. In order to assess their potential as vasodilatatory drugs in the cerebrovascular bed we have compared the relaxant effects of the classical nitrovasodilator sodium nitroprusside (SNP) and three NONOates, diethylamine/NO complex (DEA/NO), spermine/NO complex (SPER/NO), and diethylenetriamine/NO complex (DETA/NO) in isolated rabbit basilar arteries precontracted with UTP. The 4 NO donors induced full relaxation of the UTP-induced tone, with the following order of potency: SNP > DEA/NO > SPER/NO > DETA/NO. Relaxations induced by SNP and DETA/NO were not modified in rubbed (endothelium denuded) arteries in which acetylcholine-relaxations were almost abolished. On the other hand, relaxations to SNP and SPER/NO were more potent and effective in histamine-precontracted arteries than in KCl-precontracted arteries. Methylene blue significantly inhibited SPER/NO-induced relaxations in both KCl- and histamine-precontracted arteries while SNP-induced relaxations were only slightly inhibited by methylene blue in KCl-precontracted arteries. This study shows that the NO donors SNP, DEA/NO, SPER/NO and DETA/NO have quantitatively different relaxant effects in rabbit basilar arteries according to their rate of NO release. Relaxations are not mediated by endothelial factors, and are inhibited by arterial depolarization. Finally, cGMP formation is involved in relaxation induced by NONOates and much less in SNP-induced relaxation.