Astrocytomas are the most frequent primary brain tumors and constitute a leading cause of cancer-related deaths. We studied the effects of progesterone and its antagonist, RU486, on cell growth of two human astrocytoma cell lines with different evolution grade (U373, grade III; and D54, grade IV). Progesterone receptor expression was determined by Western blot. The effects of different doses of progesterone and RU486 on cell number, cell cycle, and apoptosis were analyzed for five consecutive days. Progesterone (10 nM) significantly increased the number of D54 cells from the second day of culture, and the number of U373 cells on days 3-5. RU486 (10 muM) blocked progesterone effects in both astrocytoma cell lines. Interestingly, RU486 administered without progesterone significantly reduced the number of cells from the second day of culture in both cell lines. Progesterone increased S phase of cell cycle in U373 cells (61%, on day 5). RU486 blocked the effects of progesterone on cell cycle but administered alone did not significantly change cell cycle profile. DNA fragmentation (TUNEL) assay showed that the diminution in the number of astrocytoma cells produced by RU486 was not by apoptosis. Progesterone receptor isoforms were detected in both cell lines. Our data suggest that progesterone induces cell growth of human astrocytoma cell lines through the interaction with its nuclear receptor.