Administration of vasoactive intestinal polypeptide (VIP) into the rabbit third ventricle via a permanently placed cannula resulted in a dose-dependent increase in intraocular pressure (IOP). 10P was elevated 5.2 mmHg 30 minutes after VIP (10μg/100μl) administration. Tonographic outflow facility was not altered by VIP. Thirty minutes after VIP injection into the third ventricle, aqueous humor flow estimated using the Goldmann equation was increased 36% over baseline levels. Intravenous administration of a 10 ug dose of VIP did not alter IOP. Systemic blood pressure was unaltered after third ventricle VIP. Systemic pretreatment with the cholinergic antagonist atropine blocked the VIP-induced elevation in IOP. Topical atropine pretreatment had no effect suggesting a central cholinergic mechanism for the VIP-induced increase in IOP. Physiological antagonism of the VIP response was observed after systemic pretreatment with propranolol, phentolamine, or acetazolamide.Body temperature (BT) was significantly elevated in a dose-dependent manner following central VIP administration. Indomethacin pretreatment which had no effect on the IOP response, blocked the VIP temperature response.