Gonadotropin-releasing hormone (GnRH) analogs can cause regression of uterine leiomyomata. This effect is thought to be mediated by the inhibition of gonadotropin release and steroid synthesis. In the present study we examined the possibility that these analogs may also act directly on uterine leiomyomata. Specific binding sites for GnRH are present in myoma membranes, as 125I-Buserelin binding was displaced with equal efficiency by the superagonists, Buserelin and D-Trp6-GnRH, and by the antagonist Organon 30276, but not by unrelated peptides such as thyrotropin releasing hormone and oxytocin. A nonlinear Scatchard curve obtained for Buserelin specific binding suggests the presence of at least two binding sites, one of which exhibits a relatively high affinity for GnRH analogs (Kd of approximately 10(-8) M). Western blotting with a specific GnRH receptor antibody revealed the presence of a 60 kDa protein in myoma membranes. This protein has a similar molecular weight to the purified pituitary GnRH receptor. These results indicate, for the first time, the presence of specific binding sites for GnRH in uterine leiomyomata, suggesting a direct effect of GnRH analogs on this tissue.