Studies were performed to determine the mechanism of entry of [3H]alpha-tocopherol from low density lipoprotein into cultured human fibroblasts. The cellular uptake of alpha-tocopherol at 37 degrees C was significantly different in time- and concentration-dependent experiments between normal fibroblasts and mutant fibroblasts that lack the membrane receptor for low density lipoprotein. The uptake by normal cells of both 125I-labeled low density lipoprotein and [3H]alpha-tocopherol was significantly lower at 4 degrees C where endocytosis does not occur, compared to 37 degrees C where it does occur. Also, the cellular uptake of both [3H]vitamin E and 125I-labeled low density lipoprotein was much lower when the lipoprotein was modified by methylation, which prevented its binding by the receptor, than when the native lipoprotein was measured. Although passive transfer and exchange cannot be excluded as mechanisms of entry, these data indicate that the majority of the alpha-tocopherol enters the cell with the intact lipoprotein particle. This finding is in contrast to several other hydrophobic compounds which reportedly transfer from the lipoprotein into the cell even in the absence of the lipoprotein receptor.