To determine whether heterogeneity of endothelium-dependent or independent responsiveness exists between large and small pulmonary arteries, isolated rings (3-4 mm long) from large (5-7 mm in diameter) and small (2-3 mm in diameter) intralobar pulmonary arteries were prepared from normal swine and studied in vitro. Rings, with and without endothelium, were suspended in modified Krebs-Ringer bicarbonate solution, bubbled with 95% O2-5% CO2, maintained at 37 degrees C and studied in parallel. Contractions to phenylephrine, norepinephrine and histamine were significantly potentiated in small rings, with or without endothelium, compared to large pulmonary artery rings with or without endothelium. The alpha-adrenergic agonist, UK 14304, however, caused comparable contractions in rings without endothelium taken from large and small vessels. Contractions to potassium chloride in rings without endothelium were also comparable. Relaxant responses were assessed in rings incubated with indomethacin and contracted with phenylephrine or prostaglandin F2 alpha. Acetylcholine, bradykinin, the calcium ionophore A23187 and UK 14304 elicited endothelium-dependent relaxations in rings from both large and small vessels. Relaxations induced by acetylcholine and bradykinin but not those by A23187 were significantly shifted downward in small versus large pulmonary-artery rings. Isoproterenol also caused endothelium-augmented relaxations but in rings from small vessels only. Sodium nitroprusside and nitric oxide caused similar relaxations in rings from both orders. These results demonstrate that a heterogeneity in endothelium-dependent and independent responsiveness exists between large and small pulmonary arteries.