It has been proposed that the hyperdynamic circulation found in cirrhosis is mediated by nitric oxide released through the induction of nitric oxide synthase. To investigate this the effect of the nitric oxide synthase inhibitor, N-G-monomethyl-L-arginine (L-NMMA), was studied upon the portal circulation. After a 30-min infusion of 3 mg/kg of L-NMMA there was a significant fall in heart rate from 83.2+/-4.4 to 74.2+/-3.9 bpm (p=0.005), and a significant rise in mean arterial pressure from 91.6+/-2.2 to 103.7+/-3.2 mmHg, p=0.004). There was, however, no change in hepatic venous pressure gradient (16.7+/-1.5 to 16.1+/-1.7 mmHg, p=0.477) nor in azygos venous blood flow (366+/-26 to 368+/-145 ml/min, p=0.683). On subgroups analysis by Child-Pugh grade, significant changes occurred in heart rate and mean arterial pressure only in grade A and B patients (p=0.0061 and p=00068, respectively). Regional peripheral blood how was studied using hand thermography, All patients who had anisothermic hands (relatively cold fingers compared to palmar temperature) at the start of the study developed an isothermic pattern after the L-NMMA infusion. This study demonstrates a significant systemic effect of nitric oxide synthase inhibition in patients with cirrhosis but no effect upon the portal or portosystemic collateral circulations at this dose.