Multifocal colitis associated with an epidemic of chronic diarrhea. An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea. 