Abstract--A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-Arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 µmol/L), incorporating 100 nmol/L [³H]-L-arginine for a period of 5 minutes at 37°C. Forearm [³H]-L-arginine extraction was calculated after infusion of [³H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323±43 to 1082±245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3±3.6 vs 29.0±2.1 pmol/10 000 cells per 5 minutes, respectively, at an L-arginine concentration of 300 µmol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904±434 962 vs 2 013 910±770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the L-arginine transport system.