Establishment of an active dialogue between the maternal endometrium and the implanting blastocyst is essential for successful implantation. The aim of this study was to identify genes that are explicitly expressed at implantation sites of the mouse uterus by subtractive hybridization. One expressed sequence tag of the genes identified showed 92% identity to the regulator of G-protein signalling protein 2 (RGS2). The full cDNA sequence of this gene was amplified by PCR and subsequently registered in GenBank. The sequence of its open reading frame encoding 211 amino acids was the same as that of mouse RGS2, with the exception of four amino acids. Northern blot analysis showed that the expression of this gene was much higher at implantation sites than at inter-implantation sites on days 5-8 of pregnancy. In situ hybridization localized this mRNA predominantly to the stromal cells at the implantation sites. These results indicate that RGS2 has a role during implantation, possibly by regulating the intracellular Ca(2+) mobilization and T-cell proliferation at the maternal-fetal interface.