Prooxidant-antioxidant imbalance was considered as a hallmark of age-associated, non-insulin-dependent diabetes (NIDD). The aim of this ex vivo study was to investigate possible implications of oxidative stress in the integrity and function of red blood cells (RBCs) from NIDD patients. Morphometric and analytical cytology studies were conducted. The results showed: W significant alterations of RBC ultrastructure; (ii) relevant changes of spectrin cytoskeleton; (iii) altered insulin receptor distribution; and (iv) that treatment with the antioxidizing drug N-acetylcysteine was capable of significantly counteracting these changes. These results suggest a reconsideration of RBC integrity as a possible progression marker in NIDD. (C) 2002 Elsevier Science (USA).