The amino acid L-arginine is the precursor of nitric oxide (NO), a powerful vasodilator with antiplatelet properties. The availability of L-arginine has been suggested to be a rate-limiting factor in the production of NO in conditions such as hypercholesterolemia. It was speculated that fluctuations in plasma concentrations of L-arginine during the day may be dependent upon dietary intake of the amino acid, or other variables, and might modify the elaboration of endogenous NO. Over a 24-h period, the plasma concentrations of L-arginine and NO-related compounds (NOx) were measured during an L-arginine and nitrate/nitrite-free diet (diet A) or a nitrate/nitrite-free diet with a fixed amount of L-arginine intake (3.8 g/d) (diet B) in eight healthy volunteers during a 2-day crossover study. Subjects were randomly selected to begin with diet A or diet B and consumed the other diet on the second day. During diet A, plasma L-arginine decreased significantly from 09.00 to 16.00 (21.4+/-2.0 to 11.9+/-1.1 microg/ml), rose slightly in the evening (to 16.6+/-1.7 microg/ml) and gradually increased during the night. During diet B, plasma L-arginine showed a peak after each meal (approximately 23 microg/ml). Plasma NOx concentrations measured by chemiluminescence did not show any circadian variation on either diet. Plasma L-arginine concentrations change during the day and are influenced by dietary intake. Importantly, plasma NOx do not seem to vary with this pattern in healthy individuals.