In this study we examined whether L-arginine treatment could prevent corticotropin (ACTH)-induced increases in blood pressure in the Sprague-Dawley rat. Sixty rats were randomly divided into six groups (n = 10): sham injection, ACTH injection (0.5 mg/kg per day in divided doses), L-arginine (0.6%) in food plus sham injection, L-arginine plus ACTH treatment, D-arginine (0.6%) in food plus sham injection, and D-arginine plus ACTH. Systolic pressure, water intake, urine volume, body weight, plasma and urinary electrolytes, and serum corticosterone concentrations were measured. ACTH increased systolic pressure (from 127 plus/minus 2 to 165 plus/minus 6 mm Hg, P < .001), water intake, and urine volume and decreased body weight. L-Arginine reduced ACTH-induced blood pressure rises (130 plus/minus 3 mm Hg, P < .001) but had no effect on blood pressure in sham-treated rats. D-Arginine did not affect blood pressure in sham-treated rats, and systolic pressure in D-arginine + ACTH-treated rats was similar to that of ACTH-treated rats. L-Arginine decreased serum corticosterone concentrations in sham-treated rats (424 plus/minus 43 versus 238 plus/minus 25 ng/mL, P < .01), but D-arginine had no effect. However, both drugs decreased serum corticosterone concentrations in ACTH-treated rats (1071 plus/minus 117 versus 739 plus/minus 95 and 695 plus/minus 72 ng/mL for L- and D-arginine, respectively; both P < .05). As L-arginine but not D-arginine prevented ACTH-induced increases in blood pressure in Sprague-Dawley rats and both L- and D-arginine reduced serum corticosterone concentrations in ACTH-treated rats, the effects of L-arginine in preventing ACTH-induced hypertension were not simply a consequence of decreased corticosterone secretion. (Hypertension. 1996;27:184-189.)