The types of islet cell pathology and the history and clinical course are presented for 82 patients with proven islet B-cell disease with hyperinsulinism. They form the basis for the recognition of the patient suspected of harboring this syndrome. Among laboratory tests and procedures for recognition of inappropriate hyperinsulinism, the evaluation of plasma levels of glucose (G) and immunoreactive insulin (IRI) on fasting is the most important, with calculation of the IRI/G ratio, if necessary. The determination of the concentration of basal proinsulin and C-peptide is also helpful. Suppression tests and provocative tests are used infrequently. Attempts at preoperative localization are recommended. Ultrasonography and arteriography are helpful, while transhepatic percutaneous portal venous sampling is the only procedure that can differentiate localized (solitary insulinoma) from diffuse hyperinsulinism caused by adenomatosis, hyperplasia, and nesidioblastosis (present in 18% of our patients). Intraoperative ultrasonographic localization may visualize nonpalpable tumors and exclude multiple tumors. Treatment of benign B-cell disease is primarily surgical, but a variety of drugs may be useful for temporary or more prolonged therapy.