1. Endogenous nitric oxide plays an important physiological role and i
s synthesized by several isoforms of nitric oxide synthase from the se
miessential amino acid L-arginine. Nitric oxide is detectable in the e
xhaled air of normal individuals and may be used to monitor the format
ion of nitric oxide in the respiratory tract. 2. We have investigated
the effect of orally administered L-arginine (0.05, 0.1, 0.2g/kg) comp
ared 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 dose
s of 0.1 and 0.2mg/kg, which was maximal 2h after administration. This
was associated with an increase in the concentration of L-arginine an
d nitrate in plasma, There were no significant changes in heart rate,
blood pressure or forced expiratory volume in 1 s. 4. These results su
ggest that an increase in the amount of substrate for nitric oxide syn
thase can increase the formation of endogenous nitric oxide, This may
have therapeutic relevance in diseases in which there is defective pro
duction of nitric oxide.