E coli is the most important bacterial cause of diarrhea in calves; at least 2 distinct types of diarrheal disease are produced by different strains of this organism. One type is associated with enterotoxigenic E coli, which has 2 virulence factors associated with the production of diarrhea. Fimbrial antigens enable them to attach to and colonize the villi of the small intestine. Strains in calves most commonly possess K99 (F5) or F41 fimbrial antigens, or both. These antigens are the focus of immunologic protection. Enterotoxigenic E coli also elaborate a thermostable, nonantigenic enterotoxin (Sta) that influences intestinal ion and fluid secretion to produce a noninflammatory secretory diarrhea. Diarrhea in calves and lambs also has been associated with enteropathogenic E coli that adhere to the intestine to produce an attaching and effacing lesion, with dissolution of the brush border and loss of microvillous structure at the site of attachment, a decrease in enzyme activity, and changes in ion transport in the intestine. These enteropathogens are also called “attaching and effacing E coli.” Some produce verotoxin, which may be associated with a more severe hemorrhagic diarrhea. The infection most frequently is in the cecum and colon, but the distal small intestine can also be affected. The damage in severe infections can result in edema and mucosal erosions and ulceration, leading to hemorrhage into the intestinal lumen.