To determine the presence or absence of a second form of GnRH (GnRH2) and corresponding receptor (GnRHR2) in human uterine myometrium and leiomyomata.Evaluation of human leiomyoma and patient-matched myometrium of differential mRNA and protein expression of GnRH2 and GnRHR2.University hospital.Eight women undergoing medically indicated hysterectomy for symptomatic fibroids.Microarray analysis, reverse-transcriptase polymerase chain reaction (RT-PCR), real-time RT-PCR, and immunohistochemistry.Expression of mRNA and protein in leiomyoma and patient-matched myometrium.Microarray analysis demonstrated expression, and we confirmed the findings by RT-PCR. Real-time RT-PCR demonstrated equivalent expression of the genes in leiomyoma compared with patient-matched myometrium (0.99-fold for GnRH2 and 1.28-fold for GnRHR2). Immunohistochemistry confirmed the expression of GnRH2 protein in both leiomyoma and myometrium.A second form of GnRH and corresponding receptor exists in the fibroid and myometrium. We speculate that an autocrine loop exists. Our findings provide further evidence that GnRH agonists may interact directly with GnRH receptors present in uterine fibroids.