Normal human endometrium expresses LH/hCG receptor gene. In the present study, we investigated whether human endometrial carcinomas also express this receptor gene. Reverse transcription-nested polymerase chain reaction amplified LH/hCG receptor sequences from human endometrial carcinoma just as it did those from normal human endometrium and human ovary as a positive control tissue. Northern blotting demonstrated that endometrial carcinomas contain a greater abundance of multiple LH/hCG receptor transcripts, which increased with increasing tumor grade. Western immunoblotting revealed that all grades of endometrial carcinomas contain multiple immunoreactive receptor proteins in greater abundance than normal endometrium. In situ hybridization and immunocytochemistry demonstrated not only the presence, but also higher LH/hCG receptor messenger ribonucleic acid and receptor protein levels in glands of endometrial carcinoma compared to glands in normal endometrium. Ligand blotting demonstrated that the 35-kilodalton protein receptor could bind [125I]hCG and that this binding was inhibited by excess unlabeled hCG. The binding was higher in endometrial carcinoma than in normal endometrium. Atrophic and endocervical glands from endometrial carcinoma samples contained very few or no receptors. In summary, our results demonstrate that human endometrial carcinomas not only contain but also appear to overexpress LH/hCG receptors compared to normal endometrium. This novel finding introduces previously unsuspected possibilities concerning the role of LH and its receptors in human endometrial carcinomas.