In vitro studies were undertaken to determine the reactivity and contractility of the rat main pulmonary artery (RPA) to some selected vasoactive agents. Oxytocin was found to be inactive RPA exhibited a poor responsiveness to vasopressin, acetylcholine, histamine, and bradykinin. Prostaglandins B2 and E2, K+, angiotensin, sympathomimetic agents (epinephrine and isoproterenol), 5-hydroxytryptamine (5-HT), and [Ca2+]0 were found to produce, consistently, potent and concentration-related contractions of the RPA. Pulmonary arterial strips that were precontracted with 5-HT responded with relaxations to isoproterenol in low concentrations and with contractions in high concentrations. Blockade of isoproterenol-induced relaxation by propranolol provides evidence for the existence of specific beta-adrenoceptors in RPA. The selective antagonism of contractile responses induced by epinephrine, 5-HT, acetylcholine, and histamine by phentolamine, methysergide, atropine, and pyrilamine, respectively, provides evidence for the occurrence of specific alpha-adrenergic, "D"-serotonin as well as some cholinergic (muscarinic) and H1-histamine receptors in the RPA.