The aim of the present study was to determine if low-density lipoproteins (LDLs) and red blood cell (RBC) membranes from diabetic patients present an increased susceptibility to lipoperoxidation, which might be related to the increased incidence of atherosclerosis in diabetes. LDLs and RBC membranes were isolated from 11 insulin-dependent (IDDM) and 18 non-insulin-dependent diabetic (NIDDM) patients and exposed to a peroxidative stress by incubation with phenylhydrazine. The susceptibility to peroxidation was determined by measuring the production of thiobarbituric acid-reactive substances (TBARS) after the incubation. The following parameters were also evaluated: plasma glucose, triglycerides (TG), phospholipids (PL), total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A-I, apo B, hemoglobin A1c (HbA1c), LDL PL and cholesterol, LDL fatty acid composition, and RBC membrane PL and cholesterol. Although they were apparently normolipidemic, diabetic patients showed an increased susceptibility to peroxidation in LDLs and erythrocyte membranes as compared with control subjects. The amount of arachidonic acid in LDLs and the PL concentration of RBC membranes from diabetic patients were significantly higher than in normal subjects. The increased lipoperoxidability of both RBC membranes and LDLs might play a central role in the pathogenesis of the vascular complications of diabetes mellitus.