Haemoglobin A1 (Hb A1) is becoming a routine parameter for monitoring diabetic metabolism. Although widely used, the kinetic relationship between glucose concentration and Hb A1 value is not clarified yet. In vivo biosynthesis of Hb A1 was studied in 30 patients during an oral glucose tolerance test. Ten diabetics received an i.v. injection of 0.5 g glucose/kg, 20 healthy students and infusion of 1.0 g and 1.5 g glucose/kg and hour for 6h, and six volunteers 2.0 g/kg and hour. A parallel increase and decrease of serum glucose levels and Hb A1 could be demonstrated beginning a few minutes after administration of glucose. These acute changes of Hb A1 are closely related to fluctuation of serum glucose probably representing the formation and dissociation of the labile aldimine-linkage between haemoglobin and glucose. Severe hyperglycaemia of 6 h duration is not sufficient to cause an elevation of stable glycohaemoglobin.