Endogenous nitric oxide (NO) is thought to regulate many biological functions, including pulmonary circulation and bronchomotion, and it has been found in exhaled air. Our aim was to study the excretion of NO in different parts of the respiratory system. Exhaled concentrations of NO were measured by chemiluminescence in chronic tracheostomy outpatients (group 1), in patients admitted for minor abdominal surgery (group 2), and in patients with acute respiratory failure (ARF) during mechanical ventilation (group 3). In awake volunteers (group 4), 0.57 L/min gas was aspirated through the nasal cavity into the chemiluminescence device. In group 1 (tracheostomy, n = 5) we detected 16 +/- 2 (mean +/- s.e. mean) parts per billion (ppb) NO when exhaling through the mouth, and a lower (P < 0.05) value of 4.6 +/- 0.8 ppb NO when exhaling through the tracheostomy. Before anaesthesia, group 2 (n = 11) exhibited 18 +/- 2.4 ppb NO in orally exhaled gas, increasing considerably during exhalation through the nose. Upon endotracheal intubation exhaled NO concentration dropped to 1.3 +/- 0.2 ppb (P < 0.05). In group 3 (ARF, n = 7) tracheal NO concentrations were 0.8 +/- 0.2 ppb. In group 4 (volunteers, n = 6) 394 +/- 23 ppb NO was recorded in air from the nasal cavity. In both healthy subjects and patients with respiratory failure a significant NO excretion occurs in the lower airways and lungs. The upper airways, especially the nose, contribute the largest amount of NO (> 90%) to exhaled air. The physiological implications of an upper airway source of NO remain to be defined.