The urinary concentration of pseudouridine, primarily a breakdown product of tRNA, was determined by high-performance liquid chromatography in 33 patients with small cell lung cancer (SCLC), 18 patients with non-small cell lung cancer (NSCLC), 18 patients with benign pulmonary diseases (eg, TB, COPD), and 16 healthy controls. The mean urinary pseudouridine concentration levels of the patients with SCLC, NSCLC, benign pulmonary disease and the healthy controls were 22.7 +/- 11.8, 15.6 +/- 6.0, 13.4 +/- 3.6, 12.1 +/- 3.2 nmol/mumol creatinine (mean +/- SD), respectively. The mean urinary pseudouridine concentration was significantly higher in patients with SCLC than that in patients with NSCLC, benign pulmonary disease and in the healthy controls. There was no significant difference in the urinary pseudouridine levels of patients with NSCLC and healthy controls or patients with benign pulmonary disease. Urinary pseudouridine levels above 18.5 nmol/mumol creatinine (mean value +/- 2SD for healthy controls) were noted in 54.5% of patients with SCLC, including 11 of 17 (64.7%) in extensive stage and seven of 16 (43.8%) in limited stage, and 27.8% of the patients with NSCLC. Of the 12 patients with SCLC who had follow-up urinary samples taken in series during chemotherapy courses, there was considerable urinary pseudouridine level change which paralleled the change in clinical response. Although urinary pseudouridine is not a specific marker for SCLC, it represents the tumor burden and reflects the clinical status. These findings indicate that urinary pseudouridine may be a useful tumor marker in patients with SCLC.