SUMMARY Small intestinal mucosa obtained from six fasting patientswith cholera byaperoral biopsy technique was studied with the electron microscope. The cultures of their rectal swabs were all positive for Vibrio cholerae. In the absorptive cells, large pseudopod-like cytoplasmic processes with deformed microvilli or without microvilli (blebs) projected into the intestinal lumen from the apical cell surface, interrupting the microvillous border. In the crypts some of the undifferentiated crypt cells possessed pseudopod-like cytoplasmic projections which extended into the crypt lumen. The swelling of mitochondria, the disappearance of their cristae, an increase in the number of vesicles of the Golgi apparatus, and the dilatation and vesiculation of endoplasmic reticulum were observed in the epithelial cells. The apical portion of the cells became oedematous in some of the epithelial cells. Cytoplasmic fragments enclosed by a plasma membrane, desquamated epithelial cells, cytoplasmic organelles, and secretory granules were lying free in the intestinal lumen.Marked irregular widening of the interepithelial spaces in the jejunal mucoa was observed at the midvillous area. Many cystic vacuoles were present in the cytoplasm of epithelial cells. The possibility of fluids being transported from blood vessels to intestinal lumina through the interepithelial spaces, and the significance of these pathological findings in human cholera are discussed in this study.The classic or denudation concept of the intestinal lesion in Asiatic cholera was introduced in 1879 by Virchow (1879), who demonstrated in postmortem studies the loss of mucosa from small bowel villi. This denudation concept was denied by Gangarosa, Beisel, Benyajati, Sprinz, and Piyaratn (1960) and by Fresh, Versage, and Reyes (1964) who performed intestinal biopsies in cholera patients. Several experimental models have become available to study the pathogenesis of human cholera, and produce fluid in response to intraluminal instillation of the organism or to intraluminal administration of cholera toxin. It has been shown that an exotoxin produced by Vibrio cholerae induces not only accumulation of intestinal fluid in various experimental animals but also increases in the vascular permeability in the