In support of a possible clinical use of gonadotropin-releasing hormone (Gn-RH) analogs in the treatment of the endometrial carcinoma, this study was undertaken to establish the presence and characteristics of Gn-RH receptor on endometrial cancer. Materials were human endometrial carcinomas surgically removed and endometrial carcinoma cell lines. Gn-RH receptor was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RH receptor messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (PCR) using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence. Specific Gn-RH binding sites were shown to be present in 16 of 18 well-differentiated and 4 of 7 poorly differentiated adenocarcinoma specimens (Kd = 5.89 +/- 3.59 nM, Bmax = 1.80 +/- 0.95 pmol/mg protein) and cell lines RL95-2 and HHUA with Kd of 2.38 +/- 0.86 nM. The high-affinity binding sites were also detected in six proliferative-phase endometrium (Kd = 4.24 +/- 2.32 nM, Bmax = 2.73 +/- 1.12 pmol/mg protein). Gn-RH receptor mRNA was detected in all endometrial carcinoma and endometrial specimens and cell lines where the specific binding sites were detected, but not in adenomyosis or myometrial samples. The expression of Gn-RH receptor provides a possible point of attack for therapeutic approaches using Gn-RH analogs in this malignancy.