Studies were carried out on the role of vasoactive intestinal polypeptide (VIP) in the regulation of secretion and blood flow in the rat salivary gland. The first experiments to investigate the spontaneous secretory pattern revealed a clear diurnal fluctuation with a significant increase at night, so that the subsequent experiments were performed during the daytime where the secretion was consistently low. Intravenous administration of VIP at a dose smaller than 40 pmole caused a dose-dependent vasodilatory response, but at a high dose such a local effect was hampered by a decrease in systemic blood pressure. VIP potentiated the acetylcholine chloride (AcCho)--evoked salivary secretion, but VIP (0-100 pmole/kg) alone did not cause salivary secretion. Atropine reduced the salivary secretion evoked by AcCho and VIP, and the blood flow change evoked by AcCho. However, the blood flow change evoked by VIP was not affected by atropine. Hexamethonium exerted no significant effect on the response to administration of AcCho or VIP. The results indicate that VIP has a significant vasodilatory action and cooperates with AcCho in the regulation of salivary secretion in the rat, and VIP effects are atropine resistant, as in other species of animals.