We tested the hypothesis that regulation of the pulmonary circulation by endogenous endothelin (ET) during normoxia and hypoxia was altered in conscious dogs 1 mo after left lung autotransplantation (LLA). Sham-operated control and post-LLA dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LP-) relationship. LP- plots were generated on separate days during normoxia and hypoxia (arterial PO₂ ~50 Torr) in the intact condition, after selective ET_A-receptor inhibition (BQ-485), and after combined ET_A+B-receptor inhibition (bosentan). Although LLA resulted in a chronic increase in pulmonary vascular resistance, the ET-receptor antagonists had no effect on the LP- relationship during normoxia in either group. The magnitude of hypoxic pulmonary vasoconstriction (HPV) was flow dependent in both groups, and the HPV response was potentiated post-LLA compared with control. ET_A-receptor inhibition attenuated the HPV response to the same extent in both groups. ET_A+B-receptor inhibition attenuated the HPV response to a greater extent than did ET_A-receptor inhibition alone, and this effect was greater post-LLA compared with control. Plasma ET-1 concentration only increased during hypoxia in the LLA group. These results indicate that ET does not regulate the baseline LP- relationship in either group. Both ET_A- and ET_B-receptor activation mediate a component of HPV in conscious dogs, and the vasoconstrictor influence of ET_B-receptor activation is enhanced post-LLA.