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The 1993 E. coli O157:H7 epidemic in the Western United States has provided a unique opportunity to evaluate the histopathologic temporal progression of disease in the colon in children who developed hemolytic uremic syndrome (HUS). In this report we briefly summarize the clinical courses of eight patients and then discuss the colonic pathology observed in specimens obtained at surgery or at the time of autopsy. The patients were divided into two groups: group 1 consisted of six subjects whose colonic samples were obtained during the acute phase of disease, and group 2 consisted of two subjects whose samples were obtained late in their disease. Both the gross and microscopic findings showed that the most severely affected as well as the earliest affected regions of the colon were the left and transverse portions. Only later in the disease progression was there right-sided colon involvement. These findings are in contrast to the distribution described in E. coli O157:H7 hemorrhagic colitis without HUS, thus suggesting a different mechanism of injury.