Inhibition of angiogenesis is an important new approach for cancer treatment and the research on this topic deserve special attention. 2-Methoxyestradiol (2-ME), a molecule shown to possess antiangiogenic activity, is a naturally occurring derivative of estradiol which can be potentially produced in the ovarian follicle. This study was therefore aimed firstly to asses 2-ME content in swine follicular fluid. Moreover, we evaluated the effect of this substance on VEGF production, superoxide anion generation (O(2)(-)) and superoxide dismuatase activity in granulosa cells. Our data evidence that 2-ME is present in follicular fluid where it potentially acts as a physiological inhibitor of angiogenesis by reducing VEGF production by granulosa cells: this effect could be mediated by a decrease of O(2)(-) generation.