Severe watery diarrhoea in a patient with medullary thryoid carcinoma and high calcitonin levels was associated with increased distal ileal flow. Plasma from the patient inhibited small intestinal fluid absorption in dogs without affecting mucosal cyclic AMP levels. When calcitonin was removed from the plasma, the effect in experimental bowel loops was abolished but could be restored on restitution of comparable hormone levels with pure calcitonin. These studies, combined with the failure to find evidence of increased prostaglandin activity in the patient, suggest that circulating calcitonin may be a major cause of the diarrhoea in medullary thyroid carcinoma.