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The authors designed a low-deadspace system to deliver inhaled nitric oxide from a high-concentration (10%) source. Nitric oxide, nitrogen dioxide, and O2 concentrations were compared under simulated inhaled nitric oxide therapy (in vitro) from low (0.08%, 800 ppm) and high (10%, 100,000 ppm) sources of nitric oxide in nitrogen. O2 concentrations remained above 99% and nitrogen dioxide below 3 ppm for nitric oxide delivered at dosages up to 180 ppm from the 10% source. An acute toxicity trial (in vivo) was also performed in nine rabbits mechanically ventilated with 100% O2 for four hours. Six rabbits received 80 ppm nitric oxide from a 10% source and three control rabbits received only O2. Nitric oxide, nitrogen dioxide, and O2 concentrations were monitored in the ventilator circuit. Methemoglobin, arterial blood gases, arterial blood pressure, and heart rate were sampled every hour. At the 80-ppm nitric oxide dose, an average of 1.1 +/- 0.2 ppm of nitrogen dioxide was produced within the ventilator circuit. Arterial methemoglobin in rabbits that received nitric oxide rose by 0.5% from baseline, compared with a 0.2% rise for controls (p = 0.001). The authors conclude that inhaled nitric oxide therapy can be provided from a high-concentration source. Because this system does not reduce inspired O2 fraction, it may be more appropriate than low-source-concentration nitric oxide delivery systems for testing the efficacy of inhaled nitric oxide as an adjunct to optimal conventional medical therapy.