The inhibition of lipid peroxidation of erythrocyte membranes by glutathione-dependent protection was studied in patients with non-insulin dependent diabetes mellitus. Incubation of red cells from diabetics with 1.5 mM t-butyl hydroperoxide resulted in a lipid peroxidation increase greater than that of normal controls. Glutathione-dependent and glutathione-independent protection against oxidative damage was examined using an artificial system, in which erythrocyte ghosts were incubated with t-butyl peroxide and dialysed hemolysate in the presence or the absence of 2 mM glutathione. The glutathione-dependent protection of hemolysate from diabetics was approximately 70% of that from normal controls. The results suggest that decrease in glutathione-dependent protection against lipid peroxidation, along with decrease in glutathione levels, increases oxidative damage in erythrocyte membranes taken from diabetic patients.