The effect of cadmium (Cd) on the activity of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) which play an important role in the detoxification of xenobiotics, was studied in the liver, kidney, heart and lung of Rhesus monkeys. Furthermore, the role of selenium (Se) in the modulation of Cd toxicity with respect to GST and GSH-Px was also evaluated. Cadmium exposure (5 mg Cd/kg body wt./day as CdCl2 for 10 weeks) to monkeys resulted in decreased GSH-Px activity in all four organs present in the order liver > kidney > heart > lung. Cadmium administration also resulted in a significant decrease in total GST activity present in the order liver > heart > kidney > lung, whereas a significant increase in the pi class GST activity was observed greatest in the heart followed by lung, kidney and liver. Oral administration of Se (0.5 mg Se/kg body wt./day as Na2SeO3 for 10 weeks) caused a significant increase in GSH-Px activity in the order liver > heart > kidney > lung. Selenium administration caused an increase in total GST activity in liver and lung but a decrease in kidney and heart. Simultaneous administration of Cd and Se resulted in an increase in total GST activity (except in lung) including the a class activity as well as GSH-Px activity in all four tissues under study. Thus, the mechanism by which selenium decreases Cd toxicity in Rhesus monkeys, seems to rely on the protection of the enzyme systems GST and GSH-Px in the four organs, possibly by forming non-toxic cadmium selenide.