Using a simple and rapid method, electrical potential differences across rectal and colonic mucosa have been measured at routine sigmoidoscopy in patients with irritable bowel syndrome and ulcerative colitis. In patients with irritable bowel syndrome, all of whom had diarrhoea, the mucosa was charged negatively on the luminal side and potential differences were not significantly different from those of normal subjects. In acute exacerbations of ulcerative colitis, the potential difference was reversed, the luminal side being positive. This characteristic change was seen even in mild attacks. The potential difference was usually restored to normal within a few weeks of commencing treatment. In some cases, however, it was persistently abnormal for months and failed to show the normal response to stimulation by the mineralocorticoid, fludrocortisone. The way in which measurements of potential difference can be useful in diagnosis, prognosis, and as a guide to treatment is discussed.