The red cell sorbitol concentration has been suggested as a measure of polyol pathway activity. Red cell sorbitol levels were higher in 53 patients having insulin-dependent diabetes mellitus (IDDM) than in 16 control subjects. Six patients having IDDM underwent hyperglycaemic 'clamp' studies; the red cell sorbitol level returned to the normal range when the blood glucose was clamped at 5 mmol/l for 1 h and rapidly increased when it was clamped at 15 and 25 mmol/l for a further hour at each level. Seven patients with IDDM were rendered hypoglycaemic; red cell sorbitol levels rapidly fell to a level less than, but not significantly different from normal. The results of these studies suggest that in IDDM red cell sorbitol levels are a reflection of prevailing blood glucose concentration and do not indicate long-term sorbitol accumulation in other tissues.