Vitamin E, best known as a potent antioxidant, has been shown to have other functions that are not mediated by this activity. Recent reports have suggested that vitamin E may inhibit smooth muscle cell and also cancer cell growth. We have studied the effect of dl-alpha-tocopherol (vitamin E) on a series of well-established cancer cell lines that included two erythroleukemia cell lines and a hormone-responsive breast and prostate cancer cell line. Cell proliferation was examined in these cell lines, which were maintained at optimal growth conditions. A dose-dependent inhibition of cell growth was found in all cell lines examined, with the MCF-7 breast and CRL-1740 prostate cancer cell lines showing potent suppression of growth at 0.1 mM vitamin E, whereas the erythroleukemia cell lines, HEL and OCIM-1, responded only at > 0.25 mM vitamin E with inhibition of proliferation. Studies of [3H]thymidine incorporation showed that vitamin E supplementation reduced DNA synthesis in all cell lines. Analysis of high-molecular-weight DNA revealed extensive fragmentation, indicating apoptosis of all cell lines supplemented with vitamin E. Our studies thus give evidence of a general inhibition of cell proliferation by dl-alpha-tocopherol, with breast and prostate cancer cells distinctly more sensitive than erythroleukemia cells.