Dose response studies of passive enhancement of renal allografts in the rat were performed in two major histocompatibility locus incompatible strain combinations: (DA X Lewis)F1 to Lewis and (DA X Lewis) F1 to DA. The former represents a strong incompatibility and the latter a weak incompatibility, as judged by renal allograft survival in the unmodified recipient and by the ease of specific suppression of renal allograft rejection. Doses of enhancing serum between 4 ml and 10 µl were tested. In the weaker (DA X Lewis)F1 to DA model, 50 µl were as effective as 4 ml, and resulted in complete suppression of rejection and indefinite survival, whereas 10 µl produced a partial suppression of rejection in some rats. In the stronger (DA X Lewis) F1 to Lewis model, 50 µl produced a very pronounced suppression of rejection and was only slightly less effective than 4 ml, whereas 10 µl produced significant but only feeble suppression of rejection. Thus, 50 µl is the minimum effective dose for passive enhancement. On a volume to weight basis, this corresponded to 15-20 ml/human patient. This reduces the volumes of anti-HL-A sera that are likely to be needed for the clinical application of passive enhancement to levels that can realistically be provided on a widespread basis. Furthermore, the fact that as little as 50 µl of antiserum can protect a kidney allograft from rejection makes a peripheral action of enhancing serum unlikely. Since hyperacute rejection is a peripheral phenomenon, it may be possible to use doses of antiserum sufficient to induce enhancement but insufficient to cause significant antibody-mediated graft damage.