Family history of peptic ulcer and infection with Helicobacter pylori have been identified as major risk factors for peptic ulcer disease. It is unclear, however, to what degree their impacts are independent of each other. This question was addressed in a cross-sectional study among 299 consecutive out-patients (25-54 years old) of a general practitioner. Adjusted odds ratios (95% confidence intervals) for gastroscopically verified peptic ulcer disease were 3.8 (1.4-10.1) for persons with H. pylori infection, 8.4 (2.9-24.1) for persons with a family history of ulcer, and 29.5 (6.1-143.9) for persons with both risk factors compared with persons without these risk factors. These results suggest strong, multiplicative contributions of both factors to the risk for peptic ulcer disease.