Objective: To study the expression and function of VPAC₁, VPAC₂ and PAC₁-receptors in human coronary arteries (CAs). Background: VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase activating peptide) are endogenous peptides which partially share receptors. Infusion of PACAP-38 causes migraine-like attacks, while VIP causes only mild, transient headaches. VIP and PACAP both activate VPAC₁ and VPAC₂ receptors with almost equal affinity, while PACAP has a dedicated PAC₁ receptor. This may point to PAC₁-receptor antagonism as a putative mechanism for acute or prophylactic migraine treatment, depending on the peripheral side effects. Methods: Human CAs were obtained from heart-beating donors. The fresh arteries were used in wire myograph experiments, and separate segments saved for mRNA expression studies. In the myograph setup, relaxation curves for VIP and the PACAPS vs. VPAC₁ antagonist PG-97269 or the PAC₁ antagonist PACAP(6-38) were recorded. mRNA expression of VPAC₁, VPAC₂ and PAC₁ in the arteries was studied by qRT-PCR. Results: PACAPs and VIP caused concentration-dependent relaxations of human CA, with the order of potency being VIP>PACAP-27>PACAP-38. The respective pEC50 values were 8.42±0.15, 7.66±0.24 and 7.01±0.15. PACAP(6- 38) did not induce contraction per se. PACAP(6-38) caused no significant shift in response to either agonist, while the VPAC₁-antagonist caused a reduction in the potency of VIP. mRNA for the PAC₁ receptor was present in low abundance compared to neuronal tissue. Conclusion: The predominant vasodilatory component of PACAP is mediated by VPAC-receptors. The PAC₁ receptor is present in low abundance in the coronary arteries, and antagonism causes no apparent contraction. Thus, this study suggests that if a PAC₁-receptor antagonist is employed in migraine therapy, the risk of coronary constriction as a side effect will be minor.