Carbon monoxide, a product of the heme-oxygenase (HO) pathway, is an important endogenous vasoactive substance. Production of CO has not been assessed in human cirrhosis. The aim of this study was to assess production of CO in patients with cirrhosis with and without spontaneous bacterial peritonitis (SBP). CO concentration in the exhaled air and blood carboxyhemoglobin (COHb) levels, as estimates of total HO activity, were determined in 16 healthy subjects, 32 noninfected cirrhotic patients (20 with ascites), and 19 patients with SBP, all nonsmokers. Noninfected cirrhotic patients had a CO concentration in the exhaled air and COHb levels significantly higher compared with values of healthy subjects (2.3 +/- 0.2 ppm vs. 0.7 +/- 0.1 ppm and 1.0% +/- 0.1% vs. 0.6% +/- 0.1%, respectively; P <.05 for both). Patients with ascites had the highest values. Both CO concentration in the exhaled air and COHb levels were very high in patients with SBP (5.6 +/- 0.6 ppm and 1.9% +/- 0.2%; P <.01 vs. the other 2 groups) and decreased slowly after resolution of the infection, reaching values similar to those of noninfected patients 1 month after SBP. In patients with SBP, there was a significantly direct correlation between CO and plasma renin activity (PRA) (r = 0.71, P <.001). In conclusion, these results support the existence of increased CO production in human cirrhosis, which further increases in the setting of SBP. Increased CO production may participate in the disturbance of circulatory function that occurs during severe bacterial infections in cirrhosis.