We investigated the effects of an intravenous (pentobarbital sodium) and an inhalational (halothane) general anesthetic on guanosine 3',5'-cyclic monophosphate- (cGMP) mediated pulmonary vasodilation compared with responses measured in the conscious state. Multipoint pulmonary vascular pressure-flow plots were generated in the same nine dogs in the fully conscious state, during pentobarbital sodium anesthesia (30 mg/kg iv), and during halothane anesthesia (approximately 1.2% end tidal). Continuous intravenous infusions of bradykinin (2 micrograms.kg-1.min-1) and sodium nitroprusside (5 micrograms.kg-1.min-1) were utilized to stimulate endothelium-dependent and -independent cGMP-mediated pulmonary vasodilation, respectively. In the conscious state, both bradykinin and nitroprusside decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary arterial wedge pressure) over the entire range of flows studied; i.e., bradykinin and nitroprusside caused active flow-independent pulmonary vasodilation. Pulmonary vasodilator responses to bradykinin (P less than 0.01) and nitroprusside (P less than 0.05) were also observed during pentobarbital anesthesia. In contrast, during halothane anesthesia, the pulmonary vasodilator responses to both bradykinin and nitroprusside were abolished. These results indicate that, compared with the conscious state, cGMP-mediated pulmonary vasodilation is preserved during pentobarbital anesthesia but is abolished during halothane anesthesia.