Collagenous colitis is a rare condition characterized clinically by chronic diarrhea and histologically by a thickened subepithelial collagenous band in colonic biopsies in an endoscopically normal colon. Familial occurrence of collagenous colitis has to our knowledge never been described. Here we report two families in which two first-degree related members suffered from collagenous colitis. In one family, two sisters were affected by chronic diarrhea and autoimmune disorders such as thyroid disease, rheumatoid arthritis, and pernicious anemia. Collagenous colitis was diagnosed in one of these sisters, based on colonic biopsies. Colonic biopsies of the other sister showed microscopic colitis. Review of colonic biopsies of this patient taken 11 years earlier, however, showed definite histological features of collagenous colitis. In the other family, in a father and son, both with diarrhea for several years but not suffering from any other diseases, a diagnosis of collagenous colitis was made on colonic biopsies. Human leukocyte antigen (HLA) typing showed that only the HLA A2 antigen was present in all 4 patients.