Hypoglycaemia is a relatively common cause for referral of patients to the accident and emergency departments of hospitals but most of it is iatrogenic. Occasionally, however, hypoglycaemia is due to any one of up to a hundred different disorders. In some, hypoglycaemia is the cause of intermittent neuroglycopenic symptoms that lead to their referral to medical outpatients for investigation. Only the most important are discussed here. Hyperinsulinism due to abnormal β-cell function is an uncommon but important cause of spontaneous hypoglycaemia. The diagnosis is suspected from the history of episodes of altered consciousness confirmed by demonstrating raised plasma insulin, C-peptide and proinsulin levels in peripheral blood in the presence of hypoglycaemia. Differentiation of the various causes of endogenous hyperinsulinism before surgery is difficult if not impossible and the low predictive value of most of the localizing techniques that are available makes them an additional and unnecessary cost, producing little clinical benefit. Hypoglycaemia caused by non-islet cell tumours (NICTH) is seemingly rarer than hyperinsulinism from insulinoma and tends to occur in older patients. The clinical features are similar to those of hyperinsulinism but laboratory investigation reveals appropriately depressed plasma insulin, C-peptide and proinsulin levels in the presence of hypoglycaemia. The plasma IGF-II:IGF-I ratio is characteristically high and the concentration of the E-domain of proIGF-II is raised. Autoimmune hypoglycaemia is more common in some countries than others and is most often due to autoantibodies to insulin (AIS). It may also be caused by autoantibodies to the insulin receptor and possibly to autoantibodies that are stimulatory to pancreatic β-cells. Contrary to popular belief, idiopathic reactive hypoglycaemia is rare and only one of the possible causes of the postprandial syndrome. It is characterized by a low blood glucose concentration in blood collected during a spontaneous symptomatic episode but not at other times. Its cause is unknown. Other causes of hypoglycaemia include endocrinopathies of various kinds; sepsis including malaria; congestive cardiac failure; hepatic and renal insufficiencies; diverse inborn errors of metabolism; and exogenous toxins, of which alcohol is probably the commonest. © 1993 Baillière Tindall.