Transfusion of donor blood 7 days prior to renal transplantation between certain rat strain combinations can delay subsequent graft rejection. The mechanism responsible for this increased graft tolerance remains largely unclear. In this paper it is demonstrated that IgG antibodies with affinity for cultured donor renal epithelial cells develop in the plasma of recipient PVG rats within 7 days of transplantation of a DA rat kidney. These IgG antibodies are not specific for kidney cell-restricted antigens as the activity can be completely absorbed using cells which express donor class-I MHC antigens. However, the IgG may contribute to the acute rejection of graft cells by activating antibody-dependent cell-mediated cytolytic (ADCC) mechanisms. Transfusion of donor blood 7 days prior to renal transplantation between DA and PVG rats prevented the development of IgG antibodies which bind to resting or cytokine-activated donor renal epithelial cells. Serum taken 7 days after the transplantation of animals which had been previously transfused with donor blood was not able to activate ADCC mechanisms of donor cells. The donor blood transfusion-mediated abrogation of IgG binding to graft cells may delay the onset of graft rejection by preventing antibody-dependent graft cell lysis.