Neonatal insulin-dependent diabetes mellitus (DM) is very rare and descriptions of the pancreatic pathology in affected infants vary considerably. Death after 10 months of a male child who suffered the onset of insulin-dependent DM as a neonate, together with severe diarrhea and features of the hyperimmunoglobulin E syndrome, was found to be associated with absence of islets of Langerhans. There was no evidence of any pancreatic exocrine abnormality or other endocrinopathy. Two male relatives with insulin-dependent DM have also died as infants, and after review of the literature it is suggested that this disease process may be part of the spectrum of an X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. Evidence is presented to support the suggestion that this syndrome is an autoimmune disorder.