1. Endogenous nitric oxide plays an important physiological role and is synthesized by several isoforms of nitric oxide synthase from the semiessential amino acid L-arginine. Nitric oxide is detectable in the exhaled air of normal individuals and may be used to monitor the formation of nitric oxide in the respiratory tract. 2. We have investigated the effect of orally administered L-arginine (0.05, 0.1, 0.2 g/kg) compared with matched placebo on the concentration of nitric oxide in the exhaled air in 23 normal individuals. 3. L-Arginine caused significant increases in the concentration of nitric oxide in exhaled air at doses of 0.1 and 0.2 mg/kg, which was maximal 2 h after administration. This was associated with an increase in the concentration of L-arginine and nitrate in plasma. There were no significant changes in heart rate, blood pressure or forced expiratory volume in 1 s. 4. These results suggest that an increase in the amount of substrate for nitric oxide synthase can increase the formation of endogenous nitric oxide. This may have therapeutic relevance in diseases in which there is defective production of nitric oxide.