In contrast to the "toxigenic diarrheas" caused by Vibrio cholerae and Escherichia coli, the site and mechanism of fluid loss in shigellosis are unknown. The occurrence of watery diarrhea in shigellosis suggests involvement of the small bowel. Therefore, jejunal, ileal, and colonic water and electrolyte transport was studied in Shigella flexneri 2a-infected monkeys. Infected animals fell into three groups: dysentery alone, diarrhea alone, or diarrhea and dysentery. In controls, net water, sodium, and chloride absorption was seen in the jejunum, ileum, and colon. All infected animals demonstrated diminished colonic absorption or net colonic secretion. In monkeys with dysentery alone, this was the only transport defect observed. In contrast, animals with diarrhea either alone or in combination with dysentery, exhibited net jejunum secretion. Ileal transport was normal in all animals. A severe colitis with intramucosal shigellae was seen in all symptomatic animals. In the jejunum or ileum, however, morphological changes were minimal and bacterial invasion was not seen. Therefore, unlike the "toxigenic" diarrheas," shigellosis is both a small and large intestinal disease. Mucosal invasion of the colon is essential to the development of a morphological and transport defect. Dysentery results from a colonic transport defect, while diarrhea is secondary to jejunal secretion superimposed on the defect in colonic absorption.