Background: Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS., Methods: Twelve patients with ARDS (PaO2/FIO2 180; Murray score 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines., Results: All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM., Conclusions: Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.