The aim of this study was to analyse whether some cases of unexplained infertility and implantation failure after IVF could be explained by different expression levels of the matrix metalloproteinases (MMP-2, 9), their tissue inhibitors (TIMP-2, 3) and intercellular (ICAM-1) and vascular (VCAM-1) adhesion molecules in endothelial cells. Total RNA was extracted from the endometrial tissues of 41 women (unexplained infertile, group 1, n = 15; fertile volunteers. group 2, n = 15 and patients with implantation failure after IVF, group 3, n = 11). MMP-2, MMP-9, TIMP-2, TIMP-3, ICAM-I and VCAM-I mRNA expression levels were measured quantitatively using real-time polymerase chain reaction. In the endometrium from women with unexplained infertility and implantation failure after IVF, MMP-2 and TIMP-3 expression were significantly decreased when compared with the fertile group (P < 0.05 and P <= 0.001 respectively). In addition, a marked decrease was observed in the expression of VCAM-1 in women with unexplained infertility. These results suggest that the expression of,gelatinase A (MMP-2), TIMP-3 and VCAM-1, at least at the transcriptional level, might be regulated by common factors and signalling pathways. The present study adds new and important data in this field and highlights the complex preparation of the endometrium for implantation at the molecular level.