Human leukocyte antigen (HLA) class I molecules play a central role in the immune system through either presentation of endogenous antigen and activation of T lymphocytes or functional emergence of natural killer (NK) cells. Various types of immune cells are present in the human endometrium and are believed to be involved in reproductive function and/or immunological reaction. However, little is known about the expression status and function of HLA class I molecules in the human endometrium. We therefore examined mRNA expression of HLA class I. In addition, we analysed gene expression and localization of beta2-microglobulin (beta2-MG), which is the non-variant chain of all HLA class I molecules. Compared with non-decidualized tissues, mRNA expression of both HLA class I and beta2-MG was significantly higher in decidualized endometria in the late secretory phase, under progestin treatment and during early pregnancy. Immunohistochemical studies revealed that beta2-MG was localized in decidualized endometrial stromal cells, indicating that the distribution of beta2-MG is topologically correlated with that of CD56bright+ NK cells. In-vitro culture of human endometrial stromal cells demonstrated that HLA class I mRNA was induced during the decidualization by progesterone. Accordingly, the expression of HLA class I molecules is transcriptionally activated along with decidualization of human endometrial stromal cells, and may represent an immuno-endocrine function of the endometrium.