Here we examined whether the expression of a novel immunoregulatory gene set could be used to predict outcomes in murine models of rapamycin-induced cardiac tolerance, spontaneous hepatic tolerance, and cardiac rejection. The expression of the immunoregulatory gene set was assessed with the GeXP multiplex reverse-transcription polymerase chain reaction (RT-PCR) analysis system, and it was correlated to the pathological and biochemical parameters of the allografts. In rejecting cardiac grafts, the increased expression of an inflammatory set of genes, which included CD45, CD4, CD25, suppressor of cytokine signaling 2, cytotoxic T lymphocyte-associated protein 4 (CTLA4), selectin lymphocyte, interferon-c (IFN-c), programmed cell death 1 (Pdcd1), and granzyme B (Gzmb), was seen 8 days after transplantation along with histological evidence of severe allograft rejection. In tolerant cardiac allografts, the expression of fibrinogen-like protein 2 (Fgl2), Pdcd1, killer cell lectin-like receptor G1 (Klrg1), CTLA4, and lymphocyte-activation gene 3 was associated with tolerance. In a model of liver allograft tolerance, the increased expression of lectin galactose-binding soluble 1, Fgl2, CD39, phosphodiesterase 3B, Klrg1, forkhead box P3 (Foxp3), and transforming growth factor b as well as the inflammatory set of genes was observed 8 to 14 days after transplantation (ie, when there was severe inflammatory injury). At a later time when the liver allografts had been fully accepted and were histologically normal, the expression of the inflammatory set of genes returned to the baseline, but the expression of the tolerogenic set of genes was still increased. Genes that were expressed in tolerant cardiac and liver allografts included Fgl2, Klrg1, and Foxp3, whereas genes associated with rejection included CD25, Additional Supporting Information may be found in the online version of this article.Abbreviations: CTLA4, cytotoxic T lymphocyte-associated protein 4; Ebi3, Epstein-Barr virus induced 3; Fgl2, fibrinogen-like protein 2; Foxp3, forkhead box P3; GITR, glucocorticoid-induced tumor necrosis factor-related protein; GOT, glutamate oxaloacetate transaminase; Gpr83, G protein-coupled receptor 83; GPT, glutamate pyruvate transaminase; Gzmb, granzyme B; IFN-c, interferon-c; Klrg1, killer cell lectin-like receptor G1; Lgals1, lectin galactose-binding soluble 1; mRNA, messenger RNA; MST, mean survival time; Nrp1, neuropilin 1; Nt5e, 5 0 -nucleotidase ecto; OLT, orthotopic liver transplantation; PCR, polymerase chain reaction; Pdcd1, programmed cell death 1; Pde3b, phosphodiesterase 3B; POD, postoperative day; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; RT-PCR, reverse-transcription polymerase chain reaction; Sell, selectin lymphocyte; Socs2, suppressor of cytokine signaling 2; TGF-b, transforming growth factor b; Treg, regulatory T cell.