In order to estimate the tissue liver function, tissue hepatic blood volume was measured quantitatively and non-invasively using C15O inhalation in conjunction with positron-emission tomography. Fifty-eight patients with normal liver function, 14 patients with chronic hepatitis, 28 patients with hepatic cirrhosis, and 4 patients with obstructive jaundice were studied by positron-emission tomography scan after the single breath inhalation of 20 mCi of high specific activity 15O-labeled carbon monoxide. The mean tissue hepatic blood volume was significantly greater in patients with normal livers than in patients with chronic hepatitis or hepatic cirrhosis (mean: 20.5, 18.2, and 16.1 ml per 100 cm3, respectively, p = 8.6 x 10(-8)). Tissue hepatic blood volume (tHBV) correlated with the reaction of the mesenchymal system and protein synthesis, because there was a potent correlation between tHBV and hepatic fibrosis. In normal livers, we were able to demonstrate significant differences in tissue hepatic blood volume among liver segments.