The association of cigarette smoking and other variables with the extent of the acid-secreting area and intestinal metaplasia were investigated by multivariate analysis. Studies were made by the endoscopic Congo red-methylene blue test developed in our hospital. In this test, acid-secreting areas and areas of intestinal metaplasia could be identified as discolored areas and areas staining blue with methylene blue, respectively. In multivariate analysis, the following variables were associated with a reduction in the size of the acid-secreting area in decreasing order of importance: the smoking index and age. The following factors had little or no influence on the size of the acid-secreting area: sex, and the consumption of aspirin and nonsteroidal, nonsalicylate, antiinflammatory drugs (NSNSAIDs). In general, in patients with a high smoking index, the acid-secreting area was small. Smoking had an influence in both younger and older patients and had more influence in females than in males. Multivariate analysis also shows that the following factors were associated with an increase in the area of intestinal metaplasia in decreasing order of importance: the extent of the acid-secreting area, age, and the smoking index. The following factors had little or no influence on the area of intestinal metaplasia: the consumption of aspirin and NSNSAIDs and sex. In general, in patients with little or no acid-secreting area, the area of intestinal metaplasia was extensive. These findings indicate that smoking is associated with reduction in the size of the acid-secreting area and so in development of intestinal metaplasia.