The effect of age, dietary fat type and all-rac-alpha-tocopheryl acetate (vitamin E) supplementation on ex vivo synthesis of lung eicosanoids was measured in C57BL/6NIA mice using a 2 (age) x 3 (fat) x 3 (vitamin E) factorial design. Young (3-mo-old) and old (24-mo-old) mice were fed a semipurified diet containing 5% (by wt) corn oil, coconut oil or fish oil supplemented with 30, 100 or 500 mg vitamin E/kg for 4 wk. Ex vivo synthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGI2) were measured by RIA in lung homogenates. Old mice had significantly higher concentrations of TXB2 and PGI2 than did young mice, resulting in a significant increase in the TXB2:PGI2 ratio with aging. Young and old mice fed fish oil had significantly lower concentrations of PGI2 and TXB2 than those fed corn oil or coconut oil. The degree of reduction varied according to age and vitamin E status. Old mice fed fish oil and 30 mg vitamin E/kg diet had the lowest plasma vitamin E concentration and the highest TXB2:PGI2 ratio. The TXB2:PGI2 ratio was significantly reduced in old mice fed coconut oil or fish oil by vitamin E supplementation. Vitamin E supplementation (100 mg/kg) significantly increased PGI2 concentration in young mice fed coconut oil. Thus, significant changes in the capacity of lung to synthesize eicosanoids occur with age and are influenced by dietary fat type and vitamin E. J. Nutr.