The authors hypothesized that rat plasma or tissue glutathione metabolism could change with age due to possible decreases in glutathione- related enzyme activities. To test this hypothesis, the authors measured plasma and tissue concentrations of glutathione and glutathione- related enzymes. Animals were 3 months, 12 months, or 24 months old at the time of experiments. Plasma glutathione was found to be significantly increased in both the 12-month-old and 24-month-old groups compared to the 3- month-old rats. Tissue enzyme measurements showed no significant differences between the groups in lung or liver glutathione peroxidase or glutathione S-transferase. 7-Glutamyl transpeptidase activity was significantly decreased in kidney and lung with aging. Decreases in tissue 7-glutamyl transpeptidase activity occur with age; this may contribute to increases in plasma glutathione concentrations.