We reviewed 256 mucosal biopsy specimens from the descending and sigmoid colon obtained from surgical pathology departments in several areas of the United States. Only specimens of normal colonic mucosa were included, i.e., no specimens with acute or chronic colitis or adenomatous change, or in which eosinophils invaded the crypts or muscularis mucosae. The mean number of eosinophils per intercryptal space was highest in the southern United States, and there was a 35-fold difference between the mean eosinophil concentrations of patients in New Orleans and Boston. The reason for geographic variation is unknown, but it might be related to allergens in the environment or diet. Normal variations in mucosal eosinophil concentrations should be measured within a specific region before evaluating colonic biopsy specimens for eosinophilia.