The effect of N-nitro-L-arginine (NOLA) on mean arterial pressure (AP), hindlimb vascular resistance (HVR) and heart rate (HR) was examined in conscious rabbits. 2. NOLA (15 mg kg, i.v.) increased AP (delta AP = 14 +/- 3 mmHg) and HVR (delta HVR = 0.8 +/- 0.3 U) and decreased HR (delta HR = -66 +/- 8 beats/min). AP remained elevated for at least 2 h following NOLA infusion but had returned to control levels after 24 h. In contrast, the hindlimb vaso-constriction and bradycardia were sustained for at least 48 h but had returned to control levels after 72 h. 3. In the presence of total autonomic blockade (hexamethonium 30 mg/kg; propranolol 1 mg/kg and atropine 0.1 mg/kg) NOLA continued to have a pressor (delta AP = 33 +/- 9 mm Hg) and hindlimb vasoconstrictor action (delta HVR = 0.4 +/- 0.1 U) but did not affect HR (delta HR = -1 +/- 3 beats/min). 4. NOLA has a prolonged pressor and vasoconstrictor action which is independent of any action in the central nervous system and which results in a marked reflex bradycardia. These results suggest that the peripheral biosynthesis of nitric oxide is important in regulation vascular tone and arterial pressure.