The effect of the nitric oxide (NO) synthase inhibitor, N G-nitro-l-arginine methyl ester, on gastric emptying of a non-nutrient solution was investigated in conscious rats. N G-Monomethyl-l-arginine (10 mg/kg iv) and N G-nitro-l-arginine methyl ester (3 or 10 mg/kg iv) inhibited the 20-min rate of gastric emptying of liquids by 34%, 69% and 84% respectively, whereas the 0.3 mg/kg of N G-nitro-l-arginine methyl ester or 3 mg/kg of N G-monomethyl-l-arginine had no effect. The inhibitory effect of N G-nitro-l-arginine methyl ester (3 mg/kg) was prevented by l-arginine (300 mg/kg iv), but not by d-arginine (300 mg/kg iv). N G-Nitro-l-arginine methyl ester (0.3–10 mg/kg) induced a dose-related increase in mean blood pressure up to 161±10 mm Hg. Spontaneous hypertensive rats with a mean blood pressure of 180±5 mm Hg had a gastric emptying rate of 51.9±6.1%. These data indicate that NO synthase inhibitors given iv at doses that inhibit NO synthase, delay gastric emptying through mechanisms which are unrelated to changes in arterial blood pressure.