Clinical and biochemical data are presented on 18 children with severe hyperinsulinaemic hypoglycaemia born to non-diabetic mothers. Thirteen presented within three days of birth, three by 20 months and two aged nine years. Diagnosis of hyperinsulinism (HI) was made in a single blood sample by showing inappropriate plasma insulin levels (23 +/- 3 mU/l) for glycaemia (1.2 +/- 0.1 mmol/l), with low blood ketone body, lactate, alanine and glycerol levels. All children showed increased glucose disappearance rates (KG 7.6% +/- 0.06) and glucose requirement (range, 9-25 mg/kg/min) and an exaggerated glycaemic response to glucagon when hypoglycaemic. Confirmatory tests included measurement of plasma insulin levels during leucine and arginine tolerance tests, during hypercalcaemia and after fish insulin. Coeliac angiograms were performed in three cases. Clinical progress could be divided into five categories. Four cases recovered normal insulin control spontaneously (transient neonatal HI); two children responded and remain on diazoxide therapy, two responded to diazoxide after partial pancreatectomy (diazoxide responsive HI); in three cases resolution of hypoglycaemia resulted from resection of isolated adenoma (insulinoma); total pancreatectomy was needed in five cases (nesidioblastosis) and two children were victims of drug administration (drug induced HI). This analysis allows the definition of a practical approach to diagnosis and management of this major clinical problem.