BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by airway narrowing that is most frequently inhomogeneously distributed. Ventilation/perfusion (V/Q) mismatch may explain much of the hypoxemia in patients with advanced disease. A potential treatment strategy would be to redistribute blood flow to well-ventilated lung regions in order to decrease V/Q mismatch. It has been suggested that inhaled nitric oxide (iNO) in physiologic concentrations ( approximately 100 p.p.b.) could act as a local vasodilating agent in well-ventilated lung regions. To test this, we included 10 volunteer patients with very severe COPD in this study. METHODS NO was mixed with O(2) and N(2) and administered through a face mask. The partial pressure of inspired oxygen (P(i)o(2)) did not change by more than +/- 0.5 kPa from the room air value. NO was given in 15-min periods at concentrations of approximately 0, approximately 40, approximately 400, approximately 4000 and approximately 40,000 p.p.b. (random order). During each NO exposure, arterial blood gases, methemoglobin and systemic blood pressure were measured every fifth minute. RESULTS None of the patients reported subjective effects of the different gas mixtures. The partial pressure of oxygen in arterial blood (P(a)o(2)) did not change by more than +/- 1.2 kPa from the baseline value, and there was no correlation between the change in P(a)o(2) and iNO concentration. No significant changes were found in blood pressure or methemoglobin during iNO. CONCLUSION No significant effect of iNO at concentrations up to 40,000 p.p.b. in inspired gas was found on arterial blood gases. This indicates that neither low nor high concentrations of iNO improve oxygenation in patients with very severe COPD.