To evaluate skin penetration of various vitamin E homologs, a 5% solution of either alpha-tocopherol, alpha-tocotrienol, or gamma-tocotrienol in polyethylene glycol was topically applied to SKH-1 hairless mice. After 0.5, 1, 2, or 4 h (n = four per time point and four per vitamin E homolog), the skin was washed, the animals killed, the skin rapidly removed, frozen on dry ice, and a biopsy taken and sectioned: stratum corneum (two uppermost, 5-micron sections–SC1 and SC2), epidermis (next two 10-micron sections–E1 and E2), papillary dermis (next 100 microns, PD), dermis (next 400 microns, D), and subcutaneous fat (next 100 microns, SF). SC1 contained the highest vitamin E concentrations per mu thickness. To compare the distribution of the various vitamin E forms into the skin layers, the percentage of each form was expressed per its respective total. Most surprising was that the largest fraction of skin vitamin E following topical application was found in the deeper subcutaneous layers–the lowest layers, PD (40 +/- 15%) and D (36 +/- 15%), contained the major portion of the applied vitamin E forms. Although PD only represents about 16% of the total skin thickness, it contains sebaceous glands–lipid secretory organs, and, thus, may account for the vitamin E affinity for this layer. Hence, applied vitamin E penetrates rapidly through the skin, but the highest concentrations are found in the uppermost 5 microns.