Hemoglobin A Ic is produced when glucose reacts nonenzymatically with the NH2-termini of Hb A beta chains and then undergoes an Amadori rearrangement. The concentration of Hb A Ic measured at any given time reflects a patient's mean blood glucose level for the preceding weeks to months. Infrequent measurements of Hb A Ic can therefore be used to assess long-term carbohydrate control in outpatient diabetics. In addition, the synthesis of Hb A Ic may represent a model reaction to explain the pathogenesis of many of the sequelae of chronic diabetes. Nonenzymatic glycosylation reactions may also underlie some of the changes ascribed to normal aging.