['Nitric oxide (NO) formed from L-arginine is exhaled by mammals and regulates pulmonary vascular tone. Little is known about how its formation is stimulated.', 'The concentration of NO in exhaled air was monitored by chemiluminescence in pentobarbital-anesthetized rabbits receiving mechanical ventilation by tracheostomy with graded positive end-expiratory pressure (PEEP).', 'Introduction of PEEP (2.5-15 cmH2O) elicited dose-dependent and reproducible increments in exhaled NO and in arterial oxygen tension (PaO2). The increase in exhaled NO exhibited a biphasic pattern, with an initial peak followed by a partial reversal during the 4-min period at each level of PEEP. Thus, at a PEEP of 10 cmH2O, exhaled NO initially increased from 19 +/- 4 to 30 +/- 5 parts per billion (ppb) (P < 0.001, n = 9) and then decreased to 27 +/- 5 ppb (P < 0.005) at the end of the 4-min observation period. Simultaneously, PaO2 increased from 75 +/- 12 mmHg in the control situation to 105 +/- 11 mmHg (P < 0.05) at a PEEP of 10 cmH2O. After bilateral vagotomy, including bilateral transection of the depressor nerves, the increase in exhaled NO in response to PEEP was significantly reduced (P < 0.01). Thus, after vagotomy, a PEEP of 10 cmH2O elicited an increase in the concentration of exhaled NO from 13 +/- 3 to 17 +/- 3 ppb (n = 7). Vagotomy did not affect the baseline concentration of NO in exhaled air. The PEEP-induced increments in PaO2 were not affected by the NO synthase inhibitor L-N omega-arginine-methylester (30 mg.kg-1 intravenously). In open-chest experiments, PEEP (10 cmH2O) induced a reduction in cardiac output from 317 +/- 36 to 235 +/- 30 ml.min-1 and an increase in exhaled NO from 23 +/- 6 to 30 +/- 7 ppb (P < 0.05, n = 5). Reduction in cardiac output from 300 +/- 67 to 223 +/- 52 ml.min-1 by partial obstruction of the pulmonary artery did not significantly increase exhaled NO (from 23 +/- 7 to 25 +/- 6, difference not significant; n = 3).'] Does positive end-expiratory pressure ventilation elicit increases in endogenously formed nitric oxide as detected in air exhaled by rabbits?