OBJECTIVE Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Studies on LDL oxidation in diabetes to date have examined LDL isolated from plasma, but have failed to evaluate the other pro- and antioxidant factors present in vivo, the balance of which could be crucial in determining the susceptibility of LDL to lipid peroxidation. RESEARCH DESIGN AND METHODS We examined the oxidizability of plasma from Mexican-Americans in the San Antonio Heart Study. The oxidizability of plasma in 75 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) was studied after co-incubation with a free radical initiator, 2,29-azobis-2-amidinopropane hydrochloride (AAPH). Lipid peroxide (LPO) levels were measured by a modified fluorimetrie assay. RESULTS Baseline LPO levels (μmol/l; means ± SE) were similar in the three glucose tolerance categories (NGT, 1.99 ± 0.07; IGT, 1.88 ± 0.07; NIDDM, 1.97 ± 0.07; P = 0.521). However, after incubation with AAPH (NGT, 4.30 ±0.20; IGT, 4.45 ± 0.20; NIDDM, 5.35 ± 0.20; P = 0.003), the diabetic plasma had significantly greater amounts of LPOs compared with the other two groups. There was no significant difference in LPOs between the NGT and IGT groups. The statistical significance of increased oxidizability of the diabetic plasma persisted after exclusion of patients who smoked cigarettes (n = 15) or who had vascular disease (n = 4). CONCLUSIONS In conclusion, this study shows that the plasma of Mexican-American subjects with NIDDM is more prone to lipid peroxidation than that of non-Hispanic whites