The morphology of the mucosa of orthotopic ileal bladders in place for 3 months to 4 years was studied in biopsies obtained at random from 12 patients. A mucosal flattening, a reorganization of the lining epithelium and a disappearance of the fenestrated areas of blood capillaries were found. Enterocytes progressively stratified and acquired poorly differentiated features, along with loss of microvilli, reduction of the apical fuzzy glycocalyx and enlargement of intercellular spaces. Goblet cells at short-term evaluation were actively involved in mucous synthesis and secretion. Metabolic acidosis was slight both in short-term postoperative periods-under alkaline therapy- and in long-term postoperative periods-when therapy was suspended. It can be concluded that, firstly, urine contact determines in such reservoirs a condition of acute irritation and, secondly, environmental changes induce the ileal mucosa to develop a new phenotype probably better suited to a protective rather than absorptive function.