Responses to pituitary adenylate cyclase activating polypeptide (PACAP)-38 were investigated and compared with responses to PACAP-27 and vasoactive intestinal polypeptide (VIP) in the pulmonary vascular bed of the intact-chest cat under constant flow conditions. Under low resting tone baseline conditions, injections of PACAP-38 had little or no effect on lobar arterial pressure; however, when tone in the pulmonary vascular bed was raised to a high steady level (35-40 mm Hg) with U46619, intralobar injections of PACAP-38 caused dose-related decreases in lobar arterial pressure without altering left atrial pressure. The peptide induced biphasic changes in systemic arterial pressure. PACAP-38 was more potent than VIP in decreasing lobar arterial pressure, and both peptides were significantly less potent than PACAP-27 in dilating the pulmonary vascular bed. The present data show that PACAP-38 has significant vasodilator activity in the pulmonary vascular bed of the cat, and that the 27 amino acid form of the peptide is approximately 3-fold more potent than PACAP-38.