The present study was conducted to investigate the functional implication of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC₁) receptor in the adrenal catecholamine (CA) secretion induced by either PACAP-27 or vasoactive intestinal polypeptide (VIP) in anesthetized dogs. PACAP-27, VIP, and their respective antagonists were locally infused to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by means of a high-performance liquid chromatograph coupled with an electrochemical detector. Adrenal venous blood flow was measured by gravimetry. The administration of PACAP-27 (50 ng) resulted in a significant increase in adrenal CA output. VIP (5 µg) also increased the basal CA secretion to an extent comparable to that observed with PACAP-27. In the presence of PACAP partial sequence 6-27 [PACAP-(6-27); a PAC₁ receptor antagonist] at the doses of 7.5 and 15 µg, the CA response to PACAP-27 was attenuated by ~50 and ~95%, respectively. Although the CA secretagogue effect of VIP was blocked by ~85% in the presence of PACAP-(6-27) (15 µg), it remained unaffected by VIP partial sequence 10-28 [VIP-(10-28); a VIP receptor antagonist] at the dose of 15 µg. Furthermore, the CA response to PACAP-27 did not change in the presence of the same dose of VIP-(10-28). The results indicate that PACAP-(6-27) diminished, in a dose-dependent manner, the increase in adrenal CA secretion induced by PACAP-27. The results also indicate that the CA response to either PACAP-27 or VIP was selectively inhibited by PACAP-(6-27) but not by VIP-(10-28). It is concluded that PAC₁ receptor is primarily involved in the CA secretion induced by both PACAP-27 and VIP in the canine adrenal medulla in vivo.