Human endothelial activity of ecto-5′-nucleotidase (E5′N) is several times higher than in pig endothelial cells. This may have implication for xenotransplantation due to the role this enzyme plays in conversion of pro-inflammatory and pro-aggreggatory nucleotides into anti-inflammatory and anti-aggregatory adenosine. We have shown in this study that human E5′N can be functionally expressed in pig endothelial cells leading to increased adenosine production from both extracellular AMP and ATP. We suggest that E5′N expression in transgenic pigs for xenotransplantation may help to prolong graft survival.