The effect of PACAP, a new VIP-like neuropeptide, on femoral arterial blood flow was studied in anesthetized beagle dogs. Intra-arterial infusion of PACAP38, PACAP27, or VIP (0.25-25 pmol/kg) induced a dose-related increase in femoral blood flow. The dose-response curve for PACAP27 or PACAP38 was similar to that for VIP, but the response to PACAP38 at 25 pmol/kg was significantly less than the others. The vasodilator effect of PACAP38, however, lasted three to four times longer than that of PACAP27 or VIP. Vascular effects of PACAP38 and PACAP38(COOH) did not differ. PACAP(1-15), PACAP(10-20), PACAP(27-38), and PACAP(27-38)NH2 had little effect on blood flow. Thus, PACAP38 and PACAP27 are potent VIP-like vasodilators of the femoral arterial bed in dogs; PACAP38, but not PACAP27, differs from VIP in its prolonged vasodilator effect.