The prevailing view of vitamin E (tocopherols and tocotrienols) as a health promoting agent via scavenging of radical oxygen species (ROS) has been challenged recently by reports that vitamin E is a risk factor to human health. Because of these contrasting findings, we evaluated the impact of tocopherols (TocH) on BV-2 microglial cells. Microglia are immune competent cells in the central nervous system. Administration of distinct tocopherols (a-, b-, [gamma]-, [delta]-TocH), a-TocH acid succinate, and the water-soluble synthetic Trolox, did not affect the frequency distribution of morphological cell phenotypes, but [gamma]-TocH, [delta]- TocH and a-TocH acid succinate significantly reduced the number of BV-2 cells at concentrations of more than 30 mM. Decrease in cell number was due to an increase in cell death, rather than to altered cell proliferation. Evaluation of nuclear morphology and localization of phosphatidylserine on the outer side of the plasma membrane showed an apoptotic impact of [gamma]-and [delta]-TocH, whereas a-TocH acid succinate induced necrosis in BV-2 cells. Tocopherol-induced apoptosis did not modulate caspase 3/7 activity in BV-2 cells. Surprisingly, [gamma]- and [delta]-TocH stimulated the production of ROS, which may trigger a caspase-independent cell death. Thus, our study indicates that the form of tocopherol as well as its concentration may discriminate between beneficial and detrimental impact of vitamin E.