Ongoing studies at our center on facilitating transplantation of discordant xenogeneic organs are focused on tolerance induction. To abrogate hyperacute rejection, we have used adsorption methods to eliminate natural anti-Galα1-3Gal (αGal) antibodies from the circulation of baboons. We have analyzed data concerning antibody removal in baboons that were 1) immunologically naive, 2) receiving conventional pharmacologic immunosuppressive therapy (IS), and 3) treated with a conditioning regimen for tolerance induction. We compared the efficiency of removing αGal antibody 1) by perfusion of whole blood through an αGal affinity column (CP; n=5) with 2) perfusion of plasma (separated from cellular components by apheresis) through an αGal column (CPA; n=39). Our studies demonstrate that 1) CP and CPA are equally effective in removing anti-αGal antibody, 2) CPA is the method of choice if multiple adsorptions are required, 3) CPA in naive animals transiently affects levels of total IgG and IgM, 4) four CPAs repeated at 2-4 day intervals in association with heavy IS reduce the pool of anti-αGal antibody and total Ig, and 5) splenectomy and/or IS delay the return of anti-αGal antibody.