The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined in 415 follicular fluids of 57 women participating in the IVF-ET programme in the University Women's Hospital, Marburg, in relation to the morphological appearance ("maturity") and fertilizability of harvested oocytes as well as to the levels of inhibin, FSH, IGF-1, estradiol and progesterone. Follicular aspiration was done transvaginally in all patients after down regulation with nafareline and ovarian stimulation using urofollitropin and menotropin. Ovulation was induced by hCG. ETs were measured by RIA using commercial kits supplied by Peninsula Laboratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalidated. Immunoreactive ET-1 was detectable in all follicular samples, the average level being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67.5% of the samples, the average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in the average levels of ET-1 in the fluids of small, medium and large follicles. However, there was a significantly higher level of ET-2 in the fluids of medium compared to large follicles and there was a negative correlation of the ET-2 levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could play a role during the maturation of the ovarian follicles. Unlike ET-1, the mean concentrations of ET-2 were significantly higher in the fluids with oocytes which could be fertilized and cleaved than in those with oocytes which did not fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte maturation. No correlations of ET levels were found with the levels of inhibin, FSH, estradiol and progesterone. However, ET-2 levels significantly correlated with the levels of IGF-1 (p < 0.001) indicating a possible synergistic effect of endothelins and IGF-system. In conclusion, this study is further evidence for a physiological role of the ETs in the human ovary.