Chromatographically determined haemoglobin A1c concentration was measured during short-term (1-24h) changes in glucose concentration in vitro and in vivo. In vitro at 37 degrees C the HbA1c concentration increased with glucose concentration and time both in normal and diabetic erythrocytes. In normal erythrocytes incubated in 20--100 mmol/l glucose, the increases in the HbA1c concentration were maximal after 4--6 h and then stable for the next 18--20 h. During the first hour, increases in the HbA1c concentration were linear with time and on average 0.034% HbA1c x h-1 x mmol/l glucose-1. In erythrocytes, after a rapidly produced increase (2 h), HbA1c decreased to preincubation concentrations during a further incubation of the erythrocytes in a glucose-free medium at 37 degrees C for 4--6 h. The mean rate of linear decrease was 0.017% x h-1 x mmol/l glucose-1. After incubation of erythrocytes in 100 mmol/l glucose for 24 h, 1.3% HbA1c remained stable for 6 h in saline. The rapid increase in HbA1c concentration, as determined by chromatography, was not due to stable HbA1c (ketoamine linked glucose) as no increase was found in the HbA1c concentrations determined by the thiobarbiturate method. In juvenile diabetics controlled by an artificial beta-cell, rapid changes of blood glucose concentration (up to 20 mmol/l) resulted in increases in HbA1c concentration of as much as 1.9% within 12 h (mean 1.1%). Rapid in vivo increases in HbA1c concentration were reversible by normalization of the blood glucose concentration. That rapid changes in HbA1c may occur in daily diabetic life was evidenced by differences in HbA1c concentration between blood samples from out-patient diabetics incubated in saline for 16 hours at 4 degrees C and 37 degrees C (range of differences 0.2--1.4% HbA1c). The differences correlated to the blood glucose concentration at the time of sampling blood for HbA1c determination. Thus, incubation of blood at a low glucose concentration prior to determination of the glycosylated haemoglobin concentration may overcome interference from rapidly produced HbA1c.