- The relationship between the ability of different recombinant mouse strains to reject thyroid and pancreatic islet grafts that differ in class I antigens and the frequencies of the recipients' cytolytic T lymphocyte precursors (CTL-P) directed against donor antigens was examined. We analyzed three different pairs of D region histoincompatible recombinant mouse strains in which unidirectional thyroid graft rejection occurred. Frequency analysis of their splenic CTL-P demonstrated that the mouse strains that rejected the grafts exhibit a relatively high CTL-P frequency against the donor D region-encoded alloantigens at a magnitude similar to that directed against a third party, which differ in the entire H-2 complex. Mouse strains that did not reject thyroid grafts exhibited a relatively low CTL-P frequency against the donor alloantigens, but a normal high frequency against alloantigens encoded by the entire H-2 complex of a third party strain. The effect of different routes of immunization on the two parameters was tested in B10.S(7R) mice, which accept B10.S thyroid grafts permanently. Immunization of B10.S(7R) mice by injection of 50 X 10(6) B10.S spleen cells i.p. did not confer the ability to reject B10.S thyroid grafts and did not affect the low splenic anti-B10.S CTL-P frequency. By contrast, B10.S(7R) mice that were immunized by transplantation of B10.S skin rejected a subsequent B10.S thyroid graft and at the same time demonstrated a fourfold increase in the specific CTL-P frequency. We found that the ability to reject thyroid and pancreatic islet grafts always correlated with high CTL-P frequency against the donor alloantigens; however, acceptance of allografts was not always correlated with low CTL-P frequency. We assume, therefore, that the high frequency of CTL-P against donor alloantigens may be a prerequisite (but is not always sufficient) for rejection of K/D region disparate thyroid and pancreatic islet grafts.