Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis. The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Both the 7/7-CATT repeat at position -794 and the -173 C/C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy (OR, 9.69; 95% CI, 1.29-72.5; and OR, 4.60; 95% CI, 1.05-20.2, respectively). In subjects younger than 60 years old, the number of 7-CATT alleles was significantly correlated with both the activity and inflammation scores (p=0.0079 and 0.0080, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy.