To maintain the health and beauty of their skin, con-sumers are interested in the therapeutic benefits of vitamin E (tocopherol). Since tocopherol (T) is readily oxidized, tocopheryl acetate (TAc) is frequently used in skin care products based on the premise that enzymes in the skin will bioconvert TAc to T. However, recent clinical studies (Alberts, et al. Nutr. Cancer, 1996, 26: 193) challenge this premise. Therefore, the objective of this work was to use viable, excised human skin (explants) and organotypic models (Epiderm T M , Skin 2 T M ) to examine the bioconversion of TAc to T and assess the therapeutic benefits of T.Excised human skin was obtained from cosmetic surgery and maintained at the air-liquid interface in RPMI medium. The organotypic models were maintained according to manufacturer's recommendation. All organ cultures were treated topically (4 mg/cm sq) with lotions +/- 1% TAc. Skin samples were extracted with ethanol and TAc and T were quantified by HPLC. Maximum levels of T were detected at 6 h in the Skin 2 T M model and 10 h in the skin explants. The T resulting from the metabolism of TAc is shown to mitigate peroxide-induced cell damage in the EpiDerm T M model.Our studies show: 1) human skin and organotypic models bioconvert TAc to active T, 2) T mitigates skin oxidative stress, and 3) the value of skin explant and organotypic models for studying skin metabolism and physiology.