Fresh erythrocytes obtained from senescence-accelerated mice, both prone (SAM-P/1) and resistant (SAM-R/1) strains, were separated into 4 different cell density, i. e. cell age, fractions by densitygradient centrifugation. The specific activities of pyruvate kinase and hexokinase, which are known to be marker enzymes of cell age for erythrocytes, decreased with increased erythrocyte cell density in both strains of mouse, and in some cell fractions were higher in SAM-P/1 than in SAM-R/1. The specific activity of glutathione reductase decreased with increased cell density in both strains. The specific activity of glutathione peroxidase also decreased with increased cell density in both strains, but was lower in most fractions from SAM-P/1 than in the corresponding fractions from SAM-R/1. The level of oxidized protein assessed by reactivity with 2, 4-dinitrophenylhydrazine increased with the increase in cell density in both strains of mouse and was higher in all the fractions from SAM-P/1 than in those from SAM-R/1. These results are interpreted to indicate that the aging process is accelerated in the erythrocytes of SAM-P/1, and that this acceleration is partly associated with some defect in the cellular oxidant defense mechanism, including glutathione peroxidase.