- A comparative study of allograft reaction against heart, thyroid, and skin allografts was performed using inbred congenic mouse strains. Neonatal hearts were grafted into pinna of the mouse ear, adult thyroid glands were transplanted under the kidney's capsule, and pieces of adult skin were grafted orthotopically on the dorsal side of the recipient mice. A specific mouse strain combination was chosen to serve as donors and recipients for the transplants, namely, the C57BL/6 (H-2b) and the mutant strain B6.C-H(Z1) (H-21ba), which differs in a point mutation in the K or IA region of the major histocompatibility complex. In this strain combination, an acute skin graft rejection takes place without the production of antibodies. Reciprocal skin grafts performed between C57BL/6 and B6.C-H(Z1) mice are rejected within 12 to 15 days post-transplantation, similar to the time required for the rejection of skin grafts incompatible at multiple histocompatibility loci. In contrast, neonatal cardiac transplants from C57BL/6 donors grafted to B6.C-H(Z1) recipients and vice versa were exempted from immune injury even 40 days after the transplantation, and similar results were obtained using adult thyroid transplants. Thyroid and cardiac allografts incompatible at multiple histocompatibility loci were rejected within 8 and 15 days post-transplantation, respectively. We discuss the unique antigenic characteristics of heart and thyroid grafts versus skin grafts and the possible involvement of different immune mechanisms which may explain the survival of heart and thyroid transplants compared with skin grafts. © Williams & Wilkins 1979. All Rights Reserved.