Abstract: Polyclonal anti-idiotypic antibodies (AIA) were generated against human Galα1,3Gal antibodies (anti-Gal) isolated from a single donor. Specificity of the AIA was demonstrated by selective binding to anti-Gal antibodies (Ab) and absence of reactivity to non-Gal Ab. The idiotopes identified by AIA were present on anti-Gal Ab from all of the human samples evaluated (n = 59) as well as on pooled samples, demonstrating that a restricted number of dominant idiotopes characterized the human anti-Gal Ab response. Furthermore, the AIA had cross-species reactivity with baboon serum samples (n = 19), suggesting that the overall shape of the anti-Gal Ab combining site is conserved throughout the Old World primates and providing additional evidence of the limited heterogeneity of the anti-Gal Ab repertoire. In order to evaluate the potential effect of AIA in the modulation of the anti-Gal response in vivo, a baboon was injected with repeated doses of the purified AIA. Following AIA treatment, new Ab were generated that reduced Ab-mediated cytotoxicity to porcine cells. Furthermore, administration of the AIA to a baboon prolonged the survival of intravenously infused pig hematopoietic cells when compared with their survival in a control baboon that did not receive prior AIA treatment but underwent a similar conditioning regimen.