Helicobacter pylori, non-steroidal anti-inflammatory drugs, family history, blood group O, hyperpepsinogenaemia A, alcohol and smoking have been reported to be risk factors for peptic ulcer disease. The strength of causal risk factors may differ in different populations. In 215 Japanese and 493 Dutch employees of similar age, gender and type of occupation, a structured history was obtained using a questionnaire and fasting serum samples were analysed for IgG antibodies to H. pylori and pepsinogen A all in the same laboratory. A past ulcer history was verified through case notes. We found that H. pylori seropositivity, a high serum pepsinogen A and a family history of ulcer disease were significant and independent risk factors for peptic ulcer disease. For H. pylori seropositivity there was a 20-fold increased risk among the Dutch and an eight-fold increased risk among the Japanese. The seroprevalence of H. pylori was 90% in 20 Dutch subjects with a verified ulcer history and 95% in 41 Japanese ulcer subjects; it was 29% in Dutch non-ulcer subjects and 70% in Japanese non-ulcer subjects. The cumulative difference in risk to develop peptic ulcer disease at the age of 48 years between H. pylori-infected and -uninfected subjects was 24.5-3.0 = 21.5% for the Japanese and 11.8-0.5 = 11.3% for the Dutch. Duodenal ulcer disease was associated with a high coffee consumption only among the Japanese population, where this habit was much less prevalent than among the Dutch. In conclusion, the characterization of peptic ulcer risk factors as weak or strong has no universal basis: the present study shows that from a diagnostic point of view H. pylori appears to be a weaker risk factor for peptic ulcer disease in a society with a higher seroprevalence. However, from an aetiological point of view, H. pylori has an even greater impact on ulcer morbidity in the Japanese than in the Dutch population.