The effect of pituitary adenylate cyclase activating peptide (PACAP 1-27) was examined on epithelium-intact and -denuded guinea-pig tracheal strips (GPT) and compared to vasoactive intestinal peptide (VIP) and salbutamol. PACAP (10(-11)-10(-8) moles) induced dose-dependent relaxations of the basal tone of both epithelium-intact and -denuded GPT. PACAP was approximately three times less potent than either VIP or salbutamol in relaxing epithelium-intact GPT. The relaxant effects of both peptides and salbutamol were markedly attenuated following removal of the epithelial layer. L-NAME (10(-4) M), a nitric oxide synthase inhibitor, did not affect the responses induced by either PACAP or VIP demonstrating that the relaxant effect is independent of nitric oxide synthesis. Phosphoramidon (5 x 10(-6) M) potentiated the relaxant responses of epithelium-intact GPT to both PACAP and VIP but did not affect the responses of epithelium-denuded GPT. PACAP and VIP also induced relaxations of the guinea-pig upper bronchus. In addition, PACAP (10(-6) M), as well as VIP, significantly inhibited the release of TxB2 induced by LTD4 (10(-7) M) from chopped guinea-pig lung suggesting that this newly isolated peptide, which has 68% homology with VIP, may possess anti-inflammatory action in the lung.