1. L-arginine prevents adrenocorticotrophin (ACTH)-induced hypertension in the rat. To confirm that this effect is mediated through the nitric oxide (NO) system, we examined whether N-nitro-L-arginine (NOLA) could reverse the L-arginine-induced blockade of ACTH-induced hypertension. 2. Blood pressure and metabolic parameters were examined in sham-, ACTH-, L-arginine + sham-, NOLA + sham-, ACTH + L-arginine- and ACTH + L-arginine + NOLA-treated Sprague-Dawley rats (n = 40). 3. Adrenocorticotrophin treatment increased systolic blood pressure (SBP), water intake and urine output and decreased bodyweight. N-Nitro-L-arginine alone increased SBP without affecting metabolic variables. L-Arginine alone did not affect blood pressure. The SBP was lower in L-arginine + ACTH- than ACTH-treated rats (P < 0.001), but was higher following ACTH + L-arginine + NOLA than ACTH + L-arginine (P < 0.05). 4. N-Nitro-L-arginine reversed the blood pressure-lowering effect of L-arginine in ACTH-induced hypertension in the rat, supporting the notion that NO plays a role in the hypertension.