Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.