Male ICR mice were Pair-fed semipurified diets containing 0, 55 (control), and 500 IU/kg of vitamin E. Plasma and hepatic concentrations of vitamin E were determined and found to parallel the vitamin E levels in the diet. Even though plasma vitamin E levels were virtually zero in mice fed the depleted vitamin E diet for up to 304 days, there was no statistical difference in the red blood cell fragility between these animals and controls, as determined by a hypoosmotic fragility test. The diet with enriched vitamin E concentrations also did not affect the fragility of the red blood cell (RBC). Even after 300 days of zero dietary vitamin E, mice appeared healthy, demonstrating neither neurologic dysfunction nor failure to thrive. The data indicates that mice, unlike several other species, are more resistant to vitamin E depletion and may have other mechanisms to compensate for loss of this important antioxidant.