For a number of years, the cell-damaging effects of oxidized low-density lipoproteins (LDL) have been studied. Oxidized LDL-induced tissue damage may be important in vivo; there is mounting evidence for the occurrence of oxidized lipoproteins in various pathologic conditions such as in atherosclerotic lesions and in the plasma of diabetic humans and experimental animals. These developments led to the current study of lipoprotein oxidation in streptozotocin-induced diabetes in the rat. This presentation will first review investigations of the toxicity of LDL to cells grown in tissue culture that occurs when LDL becomes oxidized. Then the results are presented indicating that lipoprotein oxidation occurs in vivo in experimental diabetes and renders diabetic lipoproteins cytotoxic in vitro. Both the oxidation and the cytotoxicity of diabetic lipoproteins are inhibitable by treating the diabetic rats with lipophilic antioxidants such as probucol.