In some COPD patients, in contrast to those with ARDS, inhaled NO reportedly worsens hypoxemia. The issue examined in this study was whether inhaled NO improves or worsens hypoxemia in humans during bronchoconstriction induced by methacholine (MCh) nebulization. Five healthy subjects and six asthma patients were recruited, and during 80 ppm NO inhalation gas exchange parameters 10 min after MCh nebulization were compared with the values obtained while breathing NO-free air. During NO inhalation, the drop in PaO2 10 min after MCh, from 95.1 +/- 5.5 (baseline; mean +/- SD) to 68.9 +/- 6.2 Torr, was greater than that under the same conditions but breathing NO-free air (from 92.6 +/- 5.3 to 79.5 +/- 11.1 Torr), and the increase in AaDO2 (from 8.9 +/- 5.4 to 29.8 +/- 5.4 Torr) was greater than that during NO-free air breathing (from 8.5 +/- 7.6 to 15.4 +/- 9.2 Torr). The SaO2 dose-response reached a plateau at 5 ppm of NO. Our results show that NO inhalation worsens desaturation during bronchospasm in humans after MCh nebulization.