Experiments were performed to investigate the influence of prostaglandins (PG) on local angiotensin II (ANG II) generation in the brain and on the blood pressure (BP) effects of brain ANG II. In indomethacin pretreated Sprague-Dawley rats renin was injected into the lateral brain ventricle. At 15 min after renin injections cerebrospinal fluid (CSF) concentrations of ANG I and ANG II were markedly and equally increased in a dose-dependent manner in the indomethacin treated and in the untreated groups. At 60 min ANG I decreased in both groups, more marked in indomethacin pretreated animals. Intracerebroventricular (ICV) injections of PGI2 induced a marked local ANG II formation in CSF without effecting plasma renin concentration. ICV renin injections were followed by dose-dependent, long lasting (greater than 2 h) BP increases. Pretreatment with indomethacin increased the BP effects of ICV renin. ICV ANG II injections increased BP. ICV pretreatment with either PGI2 or PGE1 inhibited the central ANG II pressor responses. These studies indicate that PG attenuate whereas inhibition of their biosynthesis enhances the BP effects of endogenous brain ANG II in rats. It is suggested that PG may act as inhibitory modulators of the central actions of ANG II and they may participate in feedback mechanisms of the renin angiotensin system (RAS).