Many physicians obtain a rectal biopsy from patients with irritable bowel syndrome (IBS) in order to exclude melanosis coli and collagenous or microscopic colitis. To determine the value of routine rectal biopsy in IBS, 89 patients and 59 controls were administered a bowel questionnaire, and a rectal biopsy was obtained at sigmoidoscopy. IBS patients were 82% female and averaged 44 yr. Eighty-nine percent fulfilled three or more Manning criteria, and 84% fulfilled the Rome criteria for IBS. The 59 control subjects were 37% female, and averaged 57 yr. Only 15% fulfilled three or more Manning criteria, and 5% the Rome criteria. The 148 rectal biopsies were examined histologically by a pathologist whose methods were validated by a second pathologist. Although minor changes previously reported with phosphate enemas were observed, not a single subject had melanosis coli or fulfilled criteria for microscopic or collagenous colitis. Thus, patients with an endoscopically normal colon and a diagnosis of IBS made by established criteria are unlikely to have histologic abnormalities in the rectum. Rectal biopsies are costly and unnecessary in the investigation of IBS.