Four patients with vascular headaches of remarkable severity and chronicity not responding to usual therapies brought attention to their families in which at least two members each also have Crohn's disease. Hitherto an association of Crohn's disease with vascular headache of the migrainous type has not been recognized.One patient suffered bouts of extreme constipation at age four years. When eight years old he developed “screaming, pounding headaches”. During headaches, intermittent crampy periumbilical pain and diarrhea appeared. Subsequent radiologic and surgical evidence resulted in a diagnosis of Crohn's disease. His 11-year-old brother was seen for headaches which were intractable over a period of at least six months, but bowel symptoms has not appeared as yet. Their father has Crohn's disease.A 19-year-old woman with Crohn's disease presented with headaches of the migrainous type of eight months duration, resistent to all therapies. Her mother has Crohn's disease and migraine and a sister has peptic ulcers, “gaseous colon” and migraine.Resected bowel of three of these patients showed large numbers of mast cells. We suggest that vasoactive substances, including histamine released from mast cells, could cause headache. Moreover, impaired sulfate conjugation of monamines, or decreased monoamine oxidase in diseased bowel could facilitate the absorption and increase the circulation of vasoactive substances causing headache.