OBJECTIVE To compare levels of antioxidant components of blood and aortic tissue from two strains of Japanese quail showing high and low susceptibilities to atherosclerosis and receiving either control or cholesterol-enriched diets. METHODS All experimental birds were placed on the control diet until eight weeks of age. Twenty males of each strain were then placed on the atherogenic diet (control diet supplemented with 1% cholesterol) and another 20 males of each strain were continued on the control diet for an additional 10 weeks. RESULTS In the absence of cholesterol supplementation, plasma cholesterol and triglyceride and antioxidant enzyme profiles of aorta, red blood cells and plasma were comparable in the two groups of birds, with the exception of a small, but significant (P < 0.05), decrease in aortic glutathione reductase in susceptible animals (0.378 nmol/min/mg) relative to the resistant birds (0.441 nmol/min/mg). Cholesterol feeding produced larger increases in cholesterol and triglycerides and more extensive atherosclerotic plaque formation in susceptible compared with resistant quail. In the susceptible group, significant negative correlations were noted between severity of atherosclerotic lesions and aortic superoxide dismutase (correlation coefficient -0.752) and glutathione reductase (correlation coefficient -0.775) activities. Cholesterol feeding was associated with increased activity of plasma glutathione peroxidase and superoxide dismutase activities in both strains, although only the susceptible birds showed significant positive correlations of superoxide dismutase activities with plasma cholesterol (correlation coefficient +0.694) and triglycerides (correlation coefficient +0.669). Peroxide-induced depletion of glutathione in red blood cells was unaffected by cholesterol feeding, although red blood cell susceptibility to lipid peroxidation was decreased to an equivalent degree in both strains. CONCLUSIONS Susceptible and resistant quail are biochemically distinct in terms of alterations in antioxidant components produced by dietary cholesterol supplementation. Results of the present study are consistent with the proposed involvement of oxidative processes in the pathogenesis of atherosclerosis.