In vivo transient transfection of cDNA into uterine endometrium during the implantation period provides great opportunities to analyse the physiology/pathophysiology of implantation at the molecular level. We review here methodologies which have been applied for this purpose. Viral vectors are widely used for in vivo gene therapy models; however, there is no successful example of gene transfer into the uterus using such vectors. Cationic liposome-based technologies have produced some successful results, causing alterations in implantation physiology. We applied a haemagglutinating virus of Japan envelope (HVJ-E) vector system and showed that the transfection efficiency was much higher than that of methods based on cationic liposome. Commercial HVJ-E vector (GenomONE-Neo) is now also available. Several successful examples of in vivo gene transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in determining the efficiency or timing of implantation. Based on this knowledge, we should further analyse the pathophysiology of human implantation failure using human materials.