In order to investigate the clinical usefulness of human pepsinogen I (PGI) as a noninvasive diagnostic tool for gastric lesions, 92 healthy volunteers, 87 patients with a gastric ulcer and 94 patients with gastric carcinoma, verified by histologic examinations, were enrolled. The serum level of PGI in each patient was measured by radioimmunoassay. Mean serum PGI levels were 95.4 +/- 39.4 ng/mL in patients with gastric ulcers, 77.6 +/- 29.3 ng/mL in healthy volunteers, and 52.1 +/- 26.5 ng/mL in patients with gastric carcinoma. Statistically significant differences (p < 0.01) existed between the two groups. Various factors which affect serum PGI levels, including age, sex, smoking habit, blood type, and Helicobacter pylori (H. pylori) infection, were also analyzed in each group. The serum levels of PGI were not affected by gender or blood type in any of the three groups (p > 0.05). A negative correlation of serum PGI levels with age was observed in patients with carcinoma (r = -0.43, p < 0.01). Smokers in the gastric ulcer group had significantly higher levels of PGI than nonsmokers (106.2 +/- 35.9 ng/mL vs 83.2 +/- 32.3 ng/mL, p < 0.05). A significantly higher PGI concentration was found in both H. pylori infected asymptomatic volunteers and gastric carcinoma patients (82.9 +/- 29.8 ng/mL vs 67.6 +/- 26.0 ng/mL, and 56.5 +/- 26.7 ng/mL vs 43.6 +/- 24.3 ng/mL, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)