Follicular fluid from women with endometriosis has been shown to induce a higher endometrial cell proliferation than that derived from women without the disease. To elucidate this issue further, the aims of the present study were to compare the ability of follicular fluid and peritoneal fluid to stimulate both endometrial and endometriotic cell proliferation and to verify whether the mitogenic effect was merely sex steroid-dependent. Endometrial and endometriotic cells were cultured in follicular fluid or peritoneal fluid diluted in serum-free media; the growth induced in these conditions was compared with that obtained by culturing these cells in medium supplemented with charcoal stripped calf serum and a correspondent content of 17-beta-oestradiol and progesterone. Follicular fluid was able to induce significantly higher cell proliferation than peritoneal fluid from controls, patients with endometriosis stage I-II and women with endometriosis stage III-IV (P < 0.05). Moreover, the growth in control media containing a corresponding amount of steroid hormones was significantly lower than that obtained with follicular or peritoneal fluids. This finding indicates that the stimulating effect is not simply related to the concentrations of 17-beta-oestradiol and progesterone present in these fluids. Finally, based on these results and on other previous observations, the hypothesis that follicular fluid may be involved in the development of endometriotic ovarian cysts is discussed.