Despite intensive therapeutic efforts, adult respiratory distress syndrome (ARDS) is still associated with a lethality ranging from 50 to 80%. Besides hypoxemia, fatal outcome is caused by myocardial insufficiency due to a progressive decrease in pulmonary vascular conductance. Inhalation of NO can selectively dilate pulmonary vessels in ventilated lung regions, thus increasing mean pulmonary artery conductance and decreasing venous admixture. This study determines the effects of NO inhalation in patients with severe ARDS on pulmonary gas exchange, haemodynamics and mortality. Twenty surgical patients (mean age 50.3 +/- 9.25 years) with severe ARDS (Murray score 3.4 +/- 0.3) were treated with variable concentrations of NO during mechanical ventilation with continuous positive pressure. Pulmonary artery catheters were used to measure pressures, flow and venous admixture. Mortality with NO inhalation was compared with that of previous ARDS patients (n = 20) who had not received NO. Mean duration of NO inhalation was 120.1 +/- 33.12 hours (n = 20) (range 40 to 254 hours). Mean NO concentration during the first hour of delivery was 18.5 +/- 3.88 ppm. Sixteen patients had FiO2 of 1.0 when NO was started. Within the first hour of NO inhalation, the PaO2/FiO2 ratio increased from 82.1 +/- 10.28 to 124.6 +/- 28.18. Eighteen patients were responders. Mean ventilatory pressure was lowered. Oxygenation improvement was most marked during the first 36 hours and then gradually declined. Despite the significant increase in NO related oxygenation, pulmonary artery pressures did not consistently decrease. Sixteen patients in the NO group died. In the group without NO 15 patients died. Compared with ARDS patients of similar severity not receiving NO, the NO-treated patients had the same lethality. In severe ARDS, oxygenation significantly improves with the initiation of NO inhalation, but this effect declines over time. With NO, FiO2 and ventilatory pressures can be lowered. Whether the theoretically reduced oxygen toxicity and the reduced invasiveness of mechanical ventilation with NO reduces patient mortality must be determined in larger patient groups.