Rapid fluctuation of erythrocyte sorbitol in response to the changes in plasma glucose concentration has been reported from clinical evidence. We performed more extensive in vitro and in vivo studies focussing on how fast sorbitol was accumulated and how fast the accumulated sorbitol was oxidised in response to the changes in ambient glucose concentration. Incubation studies of intact erythrocytes from healthy subjects and diabetic patients showed that erythrocyte sorbitol increased rapidly in response to increased ambient glucose concentration and the accumulated sorbitol easily decreased according to the rapid reduction of ambient glucose concentration. In addition, the higher the glucose concentration in the medium, the more erythrocytes could accumulate sorbitol. The rapid response of sorbitol levels to ambient glucose concentration was further confirmed by the results of a 75 g oral glucose tolerance test in non-diabetic subjects and diabetic patients with gastrectomy, who showed marked early hyperglycaemia caused by rapid absorption of ingested glucose and subsequent rapid reduction of plasma glucose concentration (erythrocyte sorbitol levels changed concomitantly). These findings strongly indicate that the measurement of erythrocyte sorbitol is not useful as an index of medium or long term glycaemic control.