- Thyroid graft transplantation was performed between mice of congenic strains that differ in the K or the D region. Five donor-recipient pairs of different strains were tested in each combination, and the contributions of the K and the D region gene products to thyroid graft rejection were compared. We found that thyroid cells express immunogenic H-2K and H-2D molecules, as measured by their ability to induce strong graft rejection responses. Great variability in the percentage of grafts rejected was found, however, among different pairs of congenic mice. Across D region disparities, for example, the results varied from acute thyroid graft rejection in all B10 (Db) recipients transplanted with B10.HTI (Dd) thyroid grafts, to prolonged survival of all thyroid grafts of B10.S (Ds) donors transplanted into B10.S(26R) (Db) recipient mice. To test the involvement of different genes in regulation of the immune response against class-I-disparate thyroid grafts, a D region disparity was chosen. A minimum of three different genes were found to affect the response. These genes include a non-H-2 background gene and two genes in the K/I and the D regions of the H-2 complex. The possible mechanisms by which structural and regulatory genes might affect the rejection of class-I-disparate thyroid grafts are discussed.