The possible relation between respiratory capacity and antioxidant capacity and susceptibility to oxidative stress of the liver has been investigated in Rattus norvegicus, Gallus gallus domesticus, Lacerta s. sicula, and Rana esculenta. Accordingly, we measured oxygen con- sumption and cytochrome oxidase activity, glutathione peroxidase and glutathione reductase ac- tivity and overall antioxidant capacity, and lipid peroxidation and response to oxidative stress in vitro in liver. The order of liver oxygen consumption and cytochrome oxidase activity among the different species was rat > chick > lizard > frog. The antioxidant defenses supplied by the com- bined action of glutathione peroxidase and glutathione reductase were not adapted to the respi- ratory capacities. In particular, there was no correlation either between the activities of two enzymes or between their activities and oxygen consumption. In contrast, the overall antioxidant capacity of the liver appeared to be related to its oxidative capacity, and the malondialdehyde formation, an indirect measure of lipid peroxidation, was inversely related to antioxidant capac- ity. The response to oxidative stress in vitro indicated that the liver susceptibility to oxidative challenge is higher in ectothermic than in endothermic species. Such higher susceptibility ap- peared to depend on both lower antioxidant capacity and higher levels of free radical producing species. This finding is apparently in contrast with a higher content of cytochromes in endo- therms, which are able to determine both respiratory characteristics and sensitivity to pro-oxi- dants. However, it could indicate the existence of species-related differences in the tissue content of either preventive antioxidants or hemoproteins able to trap the radicals produced at their active center. J. Exp. Zool. 284:610-616, 1999. © 1999 Wiley-Liss, Inc. It is now widely accepted that a major threat to cellular homeostasis of aerobic organisms arises from normal metabolic processes that are essential to the cell. Oxygen metabolism gener- ates as byproducts reactive oxygen species (ROS) (Chance et al., '79), which can initiate free radi- cal chain reactions eventually leading to oxida- tive damage of DNA, proteins, carbohydrates, and lipids (Kehrer, '93). The evolutionary survival pro- cesses have provided aerobic organisms with a system of biochemical defenses to neutralize the oxidative effects of reactive metabolites of oxy- gen. These biochemical defenses include both low molecular weight free radical scavengers and com- plex enzyme systems (Yu, '94). When free radical generation exceeds the antioxidant capacity of cells, oxidative stress develops. This phenomenon has been related to many pathological conditions (Halliwell and Gutteridge, '90), but it can also oc- cur as a result of normal physiological activities. Because free radical production in a biological tis- sue seems to be closely related to the oxygen con- sumption (Barja de Quiroga, '92), it is expected that oxidative stress can potentially occur when- ever the aerobic metabolic rate increases. Extensive studies have shown that the evolu- tion of homeothermy has involved a significant increase in the metabolic rate for a given body size (Dawson and Hulbert, '70; Bennet and Dawson, '76). The transition from the ectother- mic level of metabolism to the higher endother- mic level is reflected in increases in oxygen consumption (Hulbert and Else, '81; Else and Hulbert, '87) and capacity for energy production at the cellular level (Else and Hulbert, '81, '85; Christensen et al., '94). In contrast, it is not known whether a parallel increase in the cell an- tioxidant defenses have taken place to oppose the