The suitability of mouse as an animal model for studying the glutathione S-transferase (GST)-mediated detoxification mechanisms has been studied by analyzing the expression of the alpha, mu, and pi classes of glutathione S-transferase isoenzymes in mouse brain, heart, kidney, spleen, liver, and muscle. Individual isoenzymes from each of these tissues have been purified, characterized, and classified into the three known classes of GST. These studies demonstrate that GST isoenzymes are variably expressed in different mouse tissues, suggesting that their expression is tissue specific. A major isoenzyme, belonging to the pi class, with a pI value in the range of 8.6-9.1 and an approximate subunit Mr value of 22,500 was detected in each tissue investigated in this study. A variable number of mu class isoenzymes with subunit Mr values of 26,500 were expressed in all mouse tissues studied, except spleen and muscle. Only liver and kidney showed the expression of an alpha class isoenzyme, each having a basic pI value and subunit Mr of approximately 25,000. Another minor acidic alpha class isoenzyme, also with a subunit Mr value of 25,000, was detected in liver, kidney, and brain. While multiple GST isoenzymes were detected in all other tissues studied, only spleen showed the presence of a single isoenzyme, which belonged to the pi class. These results reveal considerable differences in the GST isoenzyme composition of mouse tissues as compared to rat and human tissues. However, several apparent similarities in mouse and human tissues exist, suggesting that the mouse model can be used to analyze the GST-mediated detoxification mechanisms in humans.