Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify the association of functional polymorphisms of MIF gene promoter with the development of gastro-duodenal ulcer. The study was performed in 471 stocked DNAs obtained from the subjects, including 93 healthy volunteers, with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. In all 471 DNAs, 92 and 43 were obtained from gastric and duodenal ulcer patients, respectively. By an unadjusted analysis, infection with Helicobacter pylori (H. pylori), male gender and non-steroidal anti-inflammatory drug (NSAID/aspirin) use were significantly associated with a risk for developing a gastric ulcer, whereas MIF promoter polymorphisms were not. On the other hand, infection with H. pylori, male gender and 7-CATT repeat at position -794 were significantly associated with the development of a duodenal ulcer, whereas NSAID/ aspirin use was not. By the analysis after adjustment for age, gender, NSAID/aspirin use and H. pylori infection status, 7/7-CATT homozygote had a significantly increased risk for the development of duodenal ulcers (OR, 6.31; 95% CI, 1.50-26.6; p=0.012). No factors were significantly associated with the development of peptic ulcers in NSAID/aspirin users. Our results suggested that tetranucleotide repeat polymorphism of MIF gene promoter might be associated with the development of duodenal ulcers.