Unprimed female CBA mice do not reject large (10 mm2) syngeneic male skin grafts. However, a high proportion do reject small (4 mm2) grafts. Nevertheless, rejection does not invariably result in an anamnestic response. In some cases, the immunity induced by the rejection of a small graft was overcome, and tolerance was induced by a subsequent challenge with a large graft. This suggests that the transplantation response to minor antigens is subject to active regulation, and screening of other H-2k strains indicates that the nature of the response (i.e., immunity or tolerance) is determined by a gene or genes mapping outside the major histocompatibility complex.