Two cases of polyendocrine disease occurring in sisters and presenting as intractable peptic ulcer are reported. In both cases the criteria of the Zollinger-Ellison syndrome were satisfied. One sister, aged 53, after a course of recurrent ulcer and perforation of the jejunum, died in renal failure caused by nephrocalcinosis. Abnormalities were found in the pituitary, parathyroids, pancreas, and adrenals. The other sister, aged 46, had intractable ulcer symptoms. Surgical findings indicated polyendocrine disease. She became virtually symptom-free after subtotal gastrectomy and removal of 3 pancreatic tumors. Eight other members of the family have been similarly affected. The authors believe that the Zollinger-Ellison syndrome is an expression of polyendocrine disease.