1. The influence of allogeneic pregnancies on the survival of subsequent rat renal allografts was investigated in three rat strain combinations.
2. Multiple but not single pregnancies produced significantly more long-term surviving kidney grafts than were found in virgin animals; the effect was specific for paternal antigens, as multiple pregnancies by an unrelated strain did not prolong kidney graft survival.
3. In the multiparous groups, those animals with long-surviving grafts had significantly higher levels of non-cytotoxic antibodies against paternal strain B-lymphocytes (detected by the erythrocyte antibody rosette inhibition assay) than did animals which rejected their grafts.
4. The results show that multiple pregnancies may produce a state of specific unresponsiveness to paternal antigens, similar to enhancement, which is marked by the presence of non-cytotoxic antibodies against paternal B-lymphocytes. It is suggested, therefore, that enhancement may be one of the protective mechanisms which prevent rejection of the fetus during pregnancy.