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We describe a patient with refractory sprue with malabsorption, a flat small-bowel biopsy specimen unresponsive to a gluten-free diet, and colonic biopsy specimens consistent with lymphocytic (microscopic) colitis. To investigate further the relation between celiac disease and lymphocytic or collagenous colitis (a similar and possibly related entity), we examined colorectal and small-bowel biopsy specimens in patients indexed histologically as having celiac disease who have been seen at The Johns Hopkins Hospital since 1958. Of 135 indexed patients, 21 had colorectal biopsies. Colorectal biopsy specimens were abnormal in 7 of the 21 patients. Four patients had biopsy specimens resembling lymphocytic colitis, 2 patients had acute colitis, and another patient had both lymphocytic and acute colitis. No patients had collagenous colitis. Three of the patients with lymphocytic colitis and celiac-like changes of the small bowel never responded to a gluten-free diet and may represent a distinctive panintestinal disease for which the term "lymphocytic enterocolitis" with malabsorption is proposed. [ABSTRACT FROM AUTHOR]