The recognition of porcine cells by human polyreactive natural antibody is the first step in hyperacid graft rejection and the initial obstacle to xenogeneic transplantation. Understanding this process more fully on the molecular level offers greater potential for prevention. The idiotypic crossreactivity of natural antibody suggests that a limited repertoire of VH or VL is responsible for the production of anti-porcine antibody. If this is the case then it should be possible to generate anti-idiotype reagents which can be used to characterize the pig cell reactive natural antibody population in humans and monkeys. In addition EBV transformed human B cells will be screened on the basis of production of antibodies which react with pig cells or the anti-idiotype reagents. Once monoclonal cell lines are isolated, the VH and VL will be sequenced and analyzed in order to detect any restriction of V gene usage.