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The aspect of the rectal mucosa after administration of hypertonic enemas is occasionally confused with the macroscopic appearance of quiescent ulcerative colitis. Criteria for a diagnosis of enema reaction were derived from a retrospective series and tested prospectively on 11 healthy volunteers. Photographs and biopsies were obtained before and after administration of a sodium phosphate hypertonic enema. Three observers evaluated blindly the “before” and “after” macroscopic and microscopic pictures, graded the features, and made an overall diagnosis.In random studies, two observers mistakenly classified a macroscopic picture, but all made correct histologic diagnoses of “before” and “after” biopsies. In decreasing order of discriminating power, the following features of an enema reaction were found to be useful: separation and mucous depletion of the glands (no observer variation), increase in mucosal fragility in 91 per cent of cases (82—100 per cent), edema of the lamina propria in 88 per cent (73-100 per cent), straightening of the basal membrane in 82 per cent (73-91 per cent) and an increase in extruded mucus in 70 per cent (18-100 per cent). In 39 per cent of cases (36-45 per cent), erythrocytes appeared focally in the lamina propria.The effects of hypertonic enemas can be recognized on biopsy.