Biopsy specimens of rectal mucosa from 46 consecutive patients with dysentery, from whom shigellae were isolated, were examined. On examination it appeared that the specialized epithelial cells overlying lymphoid follicles were the first to be damaged, and subsequently a vascular lesion led to detachment of epithelial cells. The vascular lesion was widespread in the lamina propria mucosae. Extensive ulceration was associated with invasion of epithelial cells by the organism. There was marked depletion of mucus and an increase in mitotic activity in the crypts. Abscesses of the crypts were rare. The only difference between patients from whom the Shiga bacillus was isolated and patients from whom other shigellae were isolated was a higher prevalence of epithelial cell detachment and luminal exudate. In patients who had been ill for greater than 1 week, cell damage of the crypts was associated with cell-mediated cytolysis, a release of cytotoxic substances from eosinophils and mast cells, and relative vascular insufficiency, all of which may contribute to persistence of dysentery.