We investigated the effects of an inhibitor of nitric oxide (NO) synthesis, N omega-nitro-L-arginine (L-NNA), on the pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs. The L-arginine analogue L-NNA (20 mg/min for 60 min iv) had no effect on the baseline pressure-flow relationship. This result indicates that tonic release of endothelium-derived relaxing factor (EDRF), which is thought to be NO or a labile NO-generating molecule, is not responsible for low resting pulmonary vasomotor tone in conscious dogs. In contrast, L-NNA caused a leftward shift in the dose-response relationship to the thromboxane mimetic U-46619, indicating that the endogenous release of EDRF modulates the pulmonary vascular response to this vasoconstrictor. Finally, after preconstriction with U-46619, L-NNA abolished the pulmonary vasodilator response to bradykinin (1-10 micrograms.kg-1.min-1) but had no effect on the pulmonary vasodilator response to sodium nitroprusside (1-10 micrograms.kg-1.min-1). Thus EDRF does not appear to tonically regulate the baseline pulmonary vascular pressure-flow relationship in conscious dogs. However, EDRF does act to attenuate the magnitude of U-46619-induced pulmonary vasoconstriction. Moreover, the pulmonary vasodilator response to bradykinin is entirely mediated by EDRF in conscious dogs.