The capacity to recognize and reject skin allografts was found to be well developed in hagfish, a very primitive vertebrate morphologically. Chronic allograft rejection characteristic of weaker histocompatibility barriers was the rule in hagfish even at a “summer” ocean temperature of 18–19 C. The sequence of observed inflammatory reactions, including lymphocyte infiltration, capillary hemorrhage, and pigment cell destruction, was typical of that seen accompanying skin allograft destruction in other vertebrates. First-set grafts showed a median survival time of 72 days compared to 28 days for second-set grafts at 18–19 C. However, when repeat grafts were placed soon after first-set rejection, acute rejection occurred after only 14 days. Accelerated second-set reactions revealed the induction of specific immunity as well as persistent immunological memory. As in higher vertebrates, such anamnesis may conversely result in enhanced survival of repeat grafts under certain conditions. Since hagfish can also give serum antibody responses to xenogeneic antigens, their usually prolonged allotransplantation reactions, like those of many more advanced vertebrates, need not necessarily be regarded as a model of immunological primitiveness.