Cross-sectional and prospective data were collected and analyzed to identify risk factors for the development of peptic ulcer disease in a population of 34,198 white, non-Hispanic Seventh-Day Adventists. On a life-style questionnaire administered in 1976, 3853 subjects reported ever having had a physician-diagnosed peptic ulcer for a lifetime prevalence of 13.5% for men and 11.0% for women. Odds ratios of greater than 2.0 (P less than 0.0001) were observed for use of "stronger pain relievers," current cigarette smoking, and history of rheumatism or other arthritis and coronary disease. For both sexes, lower but statistically significant odds ratios (P less than 0.05) were found for eating white bread, "snacking," ever having smoked cigarettes, low church involvement, poor dietary adherence, high blood pressure, rheumatoid arthritis, aspirin use, job frustration and dissatisfaction, having a "blue collar household," and having less education. During 3 years of follow-up, 154 incident cases of ulcer were identified. The average annual incidence was 1.7 per 1000. Multivariate adjusted relative risks were statistically significant for using stronger pain relievers (P less than 0.001), having rheumatic conditions (P = 0.006), and using aspirin (P = 0.013). These findings suggest that rheumatic disease and use of aspirin and stronger pain relievers are more important risk factors for development of peptic ulcer disease in certain populations than diet, life-style, or psychological or socioeconomic characteristics.