Three experiments were carried out with rats (experiments 1 and 2) and guinea pigs (experiment 3) to study the effect of oxidized fats, in interaction with dietary concentrations of vitamins E and C, on the antioxidant status of erythrocytes and the rate of haemolysis. In experiment 1, diets with fresh or thermoxidized fats, containing either 25 or 250 mg alpha-tocopherol equivalents/kg were used; experiment 2 included diets with fresh or thermoxidized fats, containing 25 mg alpha-tocopherol equivalents/kg; in experiment 3, besides a control diet with a fresh fat, diets containing thermoxidized fats with various concentrations of Vitamin E (35 vs. 175 mg alpha-tocopherol equivalent/kg) and Vitamin C (300 vs. 1000 mg/kg) were used. Rats and guinea pigs fed diets with oxidized fats had reduced concentrations of glutathione in erythrocytes as compared with animals fed the fresh fat diets. In rats fed oxidized fats, the activity of catalase and in guinea pigs fed oxidized fats, the activity of glutathione peroxidase plus the concentration of alpha-tocopherol was reduced in erythrocytes as compared with animals fed the equivalent fresh fat diets. The concentrations of alpha-tocopherol in erythrocytes were increased by both, Vitamin E and Vitamin C while the concentrations of glutathione were independent of the concentrations of those vitamins in the diets. Erythrocytes of guinea pigs fed oxidized fats also showed an increased susceptibility to haemolysis during incubation in hypotonic salt solutions; this effect could be improved by increasing the concentrations of both, Vitamin E and Vitamin C. Parameters of in vivo haemolysis (activities of lactate dehydrogenase and acidic phosphatase and concentrations of potassium and free haemoglobin in plasma) were not adversely affected in rats and guinea pigs fed the oxidized fats as compared with animals fed the fresh fats. The study shows that dietary oxidized fats reduce the antioxidant status of erythrocytes and increase their susceptibility against haemolysis but do not increase the rate of haemolysis in vivo.