Serum pepsinogen I (PGI) levels were measured in 231 duodenal ulcer (DU) patients and 100 sex- and age-comparable healthy controls. Significantly higher mean serum PGI levels were found in DU patients than in controls (124.7 +/- 3.4 ng/ml v. 92.9 +/- 2.3 ng/ml; P < 0.001) (mean +/- SE). These levels were higher in male DU patients than in female DU patients (128.5 +/- 3.9 ng/ml v. 107.4 +/- 6.4 ng/ml; P < 0.05). Smoking was associated with elevated serum PGI levels in DU patients (145.3 +/- 5.1 ng/ml v. 109.0 +/- 4.2 ng/ml; P < 0.001). Healed DUs were associated with lower mean serum PGI levels than active ulcers (110.9 +/- 7.6 ng/ml v. 129.4 +/- 3.8 ng/ml, P < 0.05). Whether patients were positive or negative for Helicobacter pylori, infection did not affect mean serum PGI levels. All the risk factors for DU may not affect serum PGI levels and DU may therefore be considered a multifactorial disease.