A 13-year-old boy with common variable hypogammaglobulinemia and type I diabetes developed a severe enteropathy that proved to be unresponsive to any treatment, including total parenteral nutrition. No evidence of known etiologies of malabsorption and/or secretory diarrhea was found in this subject. A high titer of complement-fixing enterocyte autoantibody was persistently found in the patient's serum. These features suggest that the enteropathy of this primarily immunodeficient subject had an autoimmune origin. A cycle of cyclophosphamide failed to show any amelioration of the diarrhea or a significant decrease in the autoantibody titer.