The in vitro accumulation of sorbitol by human erythrocytes incubated in a physiological glucose medium was found to be strongly reduced by the addition of ascorbic acid (AA). A maximal inhibition of sorbitol in the erythrocytes of 98.3% occurred when the concentration of AA was at its peak in the cells. After incubation, the erythrocyte sorbitol was found to be inversely correlated with the concentration of AA in the erythrocytes. A human supplementation study was conducted with 10 normoglycemic subjects. Each was given 500 mg/day AA alone or in a citrus fruit medium. Each supplementation lasted 2 wk and was followed by a 10-day washout. The citrus fruit medium produced a significantly greater increase in erythrocyte AA compared with AA alone. AA alone and in citrus fruit medium decreased erythrocyte sorbitol 12.6 and 27.2%, respectively, with the latter being significantly more effective. In a study with 4 subjects, 2000 mg/day AA resulted in a reduction in erythrocyte sorbitol of 56.1%. As in the in vitro study, there was an inverse relationship between erythrocyte AA and sorbitol. Two thousand milligrams of AA per day (AA or citrus fruit medium) was given to 8 diabetic subjects in a preliminary 3-wk supplementation trial in which erythrocyte sorbitol levels were decreased by 44.5%. These results suggest that AA supplementation for diabetic subjects may provide a simple means of preventing and ameliorating the complications of diabetes without the use of drugs.