BACKGROUND/AIMS: The relationship between nitric oxide production, endotoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis. METHODS: Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patients with cirrhosis. RESULTS: Patients with a tense ascites had higher serum nitrate levels than healthy control subjects (39 +/- 7 vs 19 +/- 4 mumol/l, p < 0.01). Patients with mild ascites and without ascites had normal values of nitrate levels. In the group of patients not treated with diuretics (n = 38), creatinine and nitrate clearances were lower in ascitic patients than in nonascitic patients (respectively 0.82 +/- 0.12 vs 1.48 +/- 0.32 ml/s, p < 0.02 and 0.30 +/- 0.07 vs 2.89 +/- 2.04 ml/s, p < 0.05). Endotoxin levels were higher in patients with cirrhosis than in control subjects and paralleled the severity of liver failure (Child A/B/C vs control subjects: 0.056 +/- 0.014/0.064 +/- 0.005/ 0.090 +/- 0.008 vs 0.027 +/- 0.005 Endotoxin Units/ml, p < 0.001). Serum nitrate levels did not correlate with endotoxemia (r = -0.110). On the other hand, levels of orosomucoid, a protein synthesized by the liver in response to a stimulation by cytokines correlated with those of nitrate (respectively r = 0.343, p < 0.01). Hemoglobin levels were negatively correlated with serum nitrate levels (r = -0.328 p < 0.02). Cardiac index was higher in patients than in control subjects and paralleled the degree of liver failure (Child A/B/C vs control subjects: 3.60 +/- 0.25/ 4.10 +/- 0.19/4.47 +/- 0.25 vs 3.15 +/- 0.12 l.min.m2, p < 0.001). Cardiac index did not correlate with serum nitrate levels, urine nitrate excretion and endotoxemia. CONCLUSIONS: Renal impairment accounts for the increased levels of serum nitrate in ascitic patients. A stimulation of nitric oxide production by cytokines may occur but endotoxemia is not involved in such a mechanism. Anemia has a role in nitric oxide activity. Nitric oxide generation assessed by nitrate in serum and urine does not seem to participate in the hyperdynamic circulatory syndrome in patients with cirrhosis.