Elevated fasting insulin concentrations and insulin resistance have been associated with non-insulin-dependent diabetes mellitus (NIDDM), obesity, atherosclerosis, and hypertension, Vitamin E supplementation in persons with and without NIDDM may be related to greater insulin sensitivity (S(I)). The cross-sectional associations of the intake of vitamins E and C with S(I) and insulin concentrations were evaluated among African American, Hispanic, and non-Hispanic white men and women with a wide spectrum of glucose tolerance included in the Insulin Resistance and Atherosclerosis Study (IRAS) (n = 1151). Insulin sensitivity was measured by minimal model analysis of a 12- sample, insulin-modified, frequently sampled intravenous glucose tolerance test. Nutrient intake (including vitamin supplement use) was assessed with a food-frequency questionnaire modified to include foods consumed by the three ethnic groups. Linear-regression models were used, including rank of S(I) and the log of fasting insulin as the outcome variables. Pearson correlation coefficients for vitamins E and C in relation to rank S(I) were r = 0.07 (P = 0.01) and r = 0.07 (P = 0.02), respectively. After adjustment for total energy and BMI these associations were no longer statistically significant and did not differ between ethnic groups. Results were similar when vitamins E and C were combined in categories of low and high antioxidant intake. Models replicated with log of fasting insulin as the outcome variable also did not produce significant associations with vitamins E or C. Thus, these cross-sectional analyses do not support the hypothesis of improved S(I) with increased intake of vitamins E and C.