A study was designed to assess the effects of a high-protein diet on the activities of several enzymes involved in the cellular antioxidative defence mechanism. Two strains of mice, a senescence-prone series (SAM-P/1) and a senescence-resistant series (SAM-R/1), were each divided into two groups, and fed either a control (20% casein) or a high-protein (40% casein) diet, respectively, for 11 months from the age of 2 months. Blood and liver were assayed for specific activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase, and the levels of oxidized protein. Ingestion of the high-protein diet decreased the specific activity of catalase in the erythrocytes from both strains of mice, and decreased that of SOD in liver from both strains of mice; however the activity of SOD in erythrocytes from SAM-R/1 was increased. In accordance with these changes, ingestion of the high-protein diet produced an increase in the level of oxidized protein, compared with ingestion the control diet, in erythrocytes from SAM-R/1, and a much more significant increase in erythrocytes from SAM-P/1. There was also an increase in the level of oxidized protein in plasma from SAM-P/1. These results are largely, if not completely, consistent with the notion that high-protein ingestion accelerates the cellular aging process by augmenting the level of oxidized protein in erythrocytes.