Pulmonary vascular responses to the K+ATP channel opener, lemakalim, were investigated in the intact-chest cat under constant flow conditions. When tone in the pulmonary vascular bed was elevated, intralobar injections of lemakalim caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. Lemakalim was approximately 3-fold more potent than cromakalim in dilating the pulmonary vascular bed, and pulmonary vasodilator responses to these K+ATP channel openers were blocked by the K+ATP channel blocking agent, glybenclamide. Glybenclamide had no significant effect on pulmonary vasodilator responses to acetylcholine or vasoactive intestinal peptide (VIP) but decreased responses to calcitonin gene-related peptide (CGRP). These data show that lemakalim has potent pulmonary vasodilator activity and suggest that responses are due to activation of a glybenclamide-sensitive K+ATP channel.