Nitric oxide (NO) has been identified as a neurotransmitter of nonadrenergic noncholinergic bronchodilator nerves. To investigate whether inhaled NO exerts a bronchodilator effect in patients with chronic obstructive pulmonary disease (COPD), we measured the resistance of the respiratory system, using the forced oscillation technique, while breathing NO. Eight patients with COPD (7 men and 1 woman; aged 66 +/- 7 yrs (mean +/- SD); forced expiratory volume in one second (FEV1) 37 +/- 17% of predicted) and eight healthy subjects (7 men and 1 woman; 33 +/- 4 yrs; FEV1 108 +/- 14% pred) were studied. Nitric oxide, at a concentration of 40 parts per million (ppm) in air, was inhaled for 20 min. Total resistance (Rrs) and reactance (Xrs) of the respiratory system, arterial oxygen saturation, heart rate, tidal volume, and breathing frequency were continuously recorded at baseline, and during and after ceasing NO inhalation. Methaemoglobin levels were additionally measured in healthy subjects. At baseline, patients with COPD showed higher Rrs than healthy subjects (Rrs at 10 Hz (Rrs,10) 4.97 +/- 2.19 vs 2.29 +/- 0.65 hPa.L-1.s). During NO inhalation, no significant change in Rrs or in Xrs was observed. Mean variation in Rrs,10 while breathing NO was negligible and similar in the two groups (-0.10 +/- 0.13 hPa.L-1.s in COPD patients and -0.02 +/- 0.13 hPa.L-1.s in healthy subjects). Moreover, there were no differences in oxygen saturation, heart rate, tidal volume and breathing frequency during NO inhalation. Methaemoglobinaemia increased at the end of NO inhalation (from 0.48 +/- 0.18 to 0.81 +/- 0.16%), and this increment remained 10 min later (0.86 +/- 0.31%). From these results, we conclude that inhaled nitric oxide, at a concentration of 40 ppm, exerts no effect on respiratory system resistance in patients with chronic obstructive pulmonary disease or in healthy subjects.