Radical-mediated oxidative damage of skeletal muscle membranes has been implicated in the fatigue process. Vitamin E (VE) is a major chain breaking antioxidant that has been shown to reduce contraction-mediated oxidative damage. We hypothesized that VE deficiency would adversely affect Muscle contractile function, resulting in a more rapid development of muscular fatigue during exercise. To test this postulate, rats were fed either a VE-deficient (EDEF) diet or a control (CON) diet containing VE. Following a 12-week feeding period, animals were anesthetized and mechanically ventilated. Muscle endurance (fatigue) and contractile properties were evaluated using an in situ preparation of the tibialis anterior (TA) muscle. Contractile properties of the TA muscle were determined before and after a fatigue protocol. The muscle fatigue protocol consisted of 60 min of repetitive contractions (250 ms trains at 15 Hz; duty cycle = I I %) of the TA muscle. Prior to the fatigue protocol, no significant differences existed in the force-frequency curves between EDEF and CON animals. At the completion of the fatigue protocol, muscular force production was significantly (P<0.05) lower in the EDEF group (reduced by 69%) compared to CON group (reduced by 38%). Following the fatigue protocol, a right shift existed in the force-frequency curve at low stimulation frequencies ( : 40 Hz) in the EDEF animals compared to the CON animals (P<0.05). The stimulated and the contralateral TA muscle from the EDEF animals had significantly higher markers of lipid peroxidation compared to the same muscles in the CON animals (P<0.05). These data support the hypothesis that VE deficiency impairs muscular endurance and alters muscle contractile properties following a prolonged series of contractions.