Normal insulin secretagogues, including glucose, usually have little influence on insulin secretion from insulinomas. Therefore, insulinomas typically cause fasting hypoglycemia with relative hyperinsulinemia. This report describes a patient with hyperinsulinemia due to an islet cell adenoma with microadenomatosis, which, upon provocative in vivo testing, was found to be profoundly responsive to hypoglycemic and hyperglycemic stimuli. A 72 hr fast followed by brisk exercise resulted in a gradual reduction of serum glucose and insulin concentrations, but did not provoke symptomatic hypoglycemia. Oral glucose tolerance testing resulted in a prompt 10-fold increase in serum insulin accompanied by a mildly symptomatic and gradual fall in serum glucose to 30 mg/dl 90 minutes after glucose ingestion. An intravenous glucose challenge caused an acute increase in serum insulin to more than 1200 μU/ml with a resulting serum glucose of 11 mg/dl 25 minutes later, associated with loss of consciousness. Although a prolonged fast has proven to be the best diagnostic test for insulin secreting tumors, many other provocative tests that use normal insulin secretagogues have been somewhat useful in this regard. The patient in this report supports the concept that insulinomas vary widely in their response to a number of normal physiologic regulators of insulin secretion, including the serum glucose concentration. A variety of provocative tests may be needed to fully evaluate the rare patient in whom there is a strong clinical suspicion of insulinoma but who has a nondiagnostic prolonged fast.