Insulinoma is a rare tumor, occurring more often in women and in the older age range. Eighty percent of patients have a single benign tumor, usually less than or equal to 2 cm in diameter, located with about equal frequency in body, head, or tail of the pancreas and amenable to surgical cure. About 10% have multiple tumors; in this group there is a high incidence of multiple endocrine neoplasia type I syndrome. The remaining 10% of patients have metastatic malignant insulinoma. Symptoms are intermittent, recur at irregular intervals in the food-deprived state over a median of 1 1/2 years, and arise from varying degrees of neuroglycopenia. Symptoms often lead to misdiagnosis as a neurologic or psychiatric disorder. Transient neurologic deficits and EEG abnormalities can be observed during hypoglycemia. Diagnosis requires repeated demonstration of hypoglycemia (glucose less than or equal to 40 mg/dl) during spontaneous or provoked symptoms, relief with ingestion of carbohydrates, simultaneous hyperinsulinemia (serum insulin greater than 6 muU/ml), and absence of insulin antibodies. A useful diagnostic adjunct is the intravenous tolbutamide test, for which new diagnostic criteria are presented.