Antibody-mediated targeting of pig costimulatory molecules is assumed to be a possible strategy to achieve donor-specific tolerance after xenotransplantation. However, porcine molecules of the B7 family (e.g. CD86) are expressed on typical antigen presenting cells (APC) and also on vascular endothelial cells. Thus, in vascularized porcine xenografts the usage of therapeutic anti-B7 monoclonal antibodies (mAb) might be associated with damage of the endothelium. Objective: In the present study we asked whether modulation of human T cell reactivity can be obtained by targeting molecules selectively expressed on pig leucocytes. Methods: MAb directed to pig CD45 were tested for their capacity to modulate the in vitro activation of human T cells induced by porcine peripheral blood mononuclear cells. Results: Porcine stimulatory cells induced significant proliferation of human T cells. In the presence of porcine CD45 mAb human T cell responses were reduced by 30–40%. The inhibitory effects were most pronounced when CD45RA mAb were used whereas mAb directed to CD45RC isoforms only moderately inhibited human T cell activation. The tested antibodies had no effects on human T cell activation induced by mitogens or by alloantigen. Conclusion: Manipulation of CD45 molecules on pig leucocytes may reduce their potential to stimulate human T cells. In recipients of vascularized porcine xenografts the usage of anti-pig CD45 mAb could be an approach to block the direct pathway of T cell activation initiated by porcine APC without affecting the endothelium of the graft.