In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10) subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after vitamin C infusion and the relative increase in plasma vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the increase in plasma vitamin C levels did not affect B cell response to glucose, but it improved Conard's K values and whole body glucose disposal in healthy subjects and in diabetic patients. In both groups of subjects vitamin C-mediated increase in insulin action was mainly due to an improvement in nonoxidative glucose metabolism. After fasting, plasma vitamin C levels correlated with basal whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C infusion, percent change in plasma vitamin C level correlated with the percent decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma vitamin C levels seem to play a role in the modulation of insulin action in aged healthy and diabetic subjects.