The urinary level of pseudouridine, primarily a degradation product of transfer ribonucleic acid (tRNA), was determined in 38 patients with primary hepatocellular carcinoma, 18 with liver cirrhosis, 12 with chronic hepatitis, nine with acute hepatitis, and 28 healthy subjects. The mean urinary pseudouridine concentration was significantly higher in the patients with hepatoma [38.2 +/- 12.8 (SD) nmol/mumol creatinine] than in those with liver cirrhosis (20.3 +/- 6.8), chronic hepatitis (24.4 +/- 8.2), and acute hepatitis (21.7 +/- 8.2), and in healthy subjects (23.8 +/- 4.9). Urinary pseudouridine level was elevated above the mean value plus 2 SD for the healthy subjects (33.6 nmol/mumol creatinine) in 71% of our hepatoma cases. Serum alpha-fetoprotein levels correlated poorly with urinary pseudouridine levels, thus, the combination assay for urinary pseudouridine and serum alpha-fetoprotein could detect 79% of the patients with hepatoma. Moreover, urinary pseudouridine level was reduced after effective transcatheter arterial embolization therapy.