The morphine-Prostigmin test has been used to diagnose disease of the sphincter of Oddi in patients with chronic abdominal pain. A twofold rise in amylase or lipase levels, reproduction of abdominal pain or both have been considered positive responses. A positive morphine-Prostigmin test has been used as a justification for a sphincteroplasty, a surgical procedure with significant morbidity. Little data are available on the response of control populations to morphine-Prostigmin, or the reproducibility of this test on different days. Ten healthy volunteers, 5 patients with symptoms of irritable bowel syndrome and 4 patients with chronic abdominal pain were given the morphine-Prostigmin test. Sixty percent of our healthy control subjects and patients with the irritable bowel syndrome had a marked elevation in amylase and lipase. Forty percent of those with the irritable bowel syndrome had reproduction of their typical abdominal pain after morphine-Prostigmin. Two of four patients with chronic abdominal pain had a different response to morphine-Prostigmin on second as compared to initial testing. We conclude that: (a) neither enzyme rise nor reproduction of abdominal pain produced by morphine-Prostigmin are specific for disease of the sphincter of Oddi, and (b) the morphine-Prostigmin test may give different results on different days in the same patient. Major clinical decisions should not be made on the basis of this test.