To investigate whether human endometrial stromal cells (ESCs) express the interferon-gamma-receptor (IFN-gamma R) and whether the process of decidualization or human chorionic gonadotropin (hCG) regulate the IFN-gamma R and its signaling pathway. In vitro experiment. Research laboratory at a medical university center. Premenopausal women undergoing hysterectomy for benign reasons. Isolation and incubation of ESCs from hysterectomy specimens with 17beta-estradiol, progesterone, recombinant hCG, and IFN-gamma as well as an IFN-gamma R-blocking antibody. We analyzed IFN-gamma R and the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) by flow cytometry. We measured IFN-gamma R and interferon response factor 1 (IRF-1) mRNA using semiquantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The IFN-gamma R is up-regulated in human ESCs during decidualization without affecting the phosphorylation of STAT-1. Stimulation of IRF-1 by IFN-gamma is reduced in decidualized ESCs. We found that hCG neither regulates the IFN-gamma R nor its signaling pathway. These results show an inverse regulation of the IFN-gamma R and its signaling response via STAT-1 and IRF-1 in human ESCs during decidualization. The early embryonic signal hCG has no effect on this process. This mechanism may finely modulate the reactivity of ESCs to IFN-gamma-mediated signals from immune cells at the implantation site.