Experiments were carried out in conscious, unrestrained, male rats to evaluate possible interactions between brain prostanoids and the brain renin-angiotensin system in the control of vasopressin release and in cardiovascular regulation. The intracerebroventricular (icv) administration of prostaglandin D2 (PGD2) resulted in transient increases in the plasma vasopressin concentration (PAVP) and heart rate and a gradual increase in mean arterial blood pressure (MABP). Pretreatment icv with saralasin, an angiotensin II-receptor antagonist, moderately attenuated the vasopressin response to PGD2, but had no effect on the heart rate and blood pressure responses. Angiotensin II icv increased both PAVP and MABP. This vasopressin response was almost completely prevented by prior icv meclofenamate, a cyclooxygenase inhibitor, and the blood pressure response was attenuated. These observations, combined with previous studies of the role of central angiotensin II and central prostanoids in the physiological control of vasopressin release, suggest that there may be important interactions between brain prostanoids and the brain renin-angiotensin system in this control.