1. In order to investigate possible species-related variations in antioxidant capacity, the susceptibility of red cells from various species (e.g. rat, rabbit, pig and quail) to depletion of glutathione (GSH) and formation of malondialdehyde (MDA), an indirect measure of lipid peroxidation, following in vitro oxidative challenge with t-butylhydroperoxide (tBHP) has been examined. 2. Marked differences in sensitivity were found, although the relative order of susceptibilities varied depending on the index of oxidation used. 3. For example, pig erythrocytes showed the highest sensitivity to depletion of GSH but the greatest resistance to tBHP-induced MDA formation. 4. Red cell susceptibility to oxidative stress under the experimental conditions used was not predictable from basal levels of GSH or from the activities of antioxidant enzymes, suggesting a prominent role of non-enzymatic antioxidants. 5. Species-dependent differences in antioxidant capacity were also found to extend to myocardial tissue homogenates and some degree of parallelism was noted with tBHP-induced MDA formation in red cells of the same species. 6. Thus, the relative resistance of both tissues from pig contrasted with the high susceptibility of red cells and myocardium from rat and quail. 7. This parallelism allows the suggestion that the functional consequences of antioxidant interventions might be discernible from measurements involving red cells. 8. Our findings may have potentially important implications in the interpretation and comparison of data obtained with experimental models of disease states in which oxidative processes are implicated when differences in species are involved.