A regimen of immunosuppressive chemotherapy which readily permits long-term survival of renal homografts fails to permit long-term survival of skin grafts. The relatively long survival of kidney compared with skin may be due to some antigenic peculiarities of the two tissues, anatomic features of the graft-host relationship, or host response to the two tissues. When skin and kidney grafts from the same donor are placed simultaneously, there is a significant prolongation of skin survival and a dramatic decrease in renal homograft survival. An experimental analysis of this unexpected finding shows that prolonged skin graft survival in the presence of a kidney is not the result of uremia or unrecognized variations in drug dosage. Evidence suggests that skin stimulates the host-immune system to produce individual-specific antibodies which are cleared from the circulation by the kidney, resulting in destruction of the kdney and preservation of the skin.