2-Methoxyestradiol (2ME), a metabolite deriving from 17-? estradiol, is a well-established antiangiogenic, apoptotic and antiproliferative agent in cell cultures and animal models. 2ME may also exert its cytotoxic activity by interacting with tubulin and by causing an impairment of the microtubular system. In this study was investigated the relative effectiveness of 2ME on glial and neural cell cultures in inducing morpho-functional changes and alteration of the microtubular system physiology. Results demonstrate that 2ME is more effective in neural cells than in glial cells. Moreover, the cytoxic activity of 2ME in both cell lines could be strictly related to an impairment of microtubule system physiology resulting in morpho- functional changes, block of mitosis and cell death.