Regeneration of rectal mucosa after rectal mucosectomy and ileoanal anastomosis (IAA) could jeopardize the long-term safety of the procedure. The aim of this study was to determine if rectal mucosal regeneration occurred after IAA. Pathologic specimens of the IAA and surrounding rectal muscular cuff were obtained from 29 patients who had required IAA excision 17±2 months (mean±SEM, range, 2 to 48 months) following construction. Multiple (≥6) coronal and sagittal sections of each specimen were made and examined histologically. The rectal muscle cuff was bound to ileal serosa by dense fibrous tissue. Small islets of residual rectal mucosa were identified between the denuded rectal cuff and the ileal pull-through in four patients (14 percent) and at the ileoanal anastomosis in two patients (7 percent). Active rectal muscosal disease, dysplasia, or reeplithelialization of the denuded rectal muscle were not seen. It is concluded that small islets of rectal mucosa may remain after IAA. Up to four years after IAA, however, no evidence of rectal mucosal regeneration could be documented.