T-cell immune response cDNA 7 (TIRC7) is a recently described T-cell costimulatory molecule that exhibits a central role in T-cell activation in vitro and in vivo. The present study was undertaken to investigate association between intragraft and peripheral blood mononuclear cell (PBMC) TIRC7 mRNA levels and cardiac allograft rejection in humans. TIRC7 gene expression levels were determined by a quantitative-competitive reverse transcriptase-polymerase chain reaction (QC-RT-PCR) in endomyocardial biopsies and in PBMC from cardiac transplant recipients. Biopsies collected during rejection or up to 15 days before rejection showed heightened TIRC7 mRNA expression in comparison with biopsies without rejection. All prerejection and rejection biopsies showed TIRC7 mRNA upregulation, while this was present in only 30% of the biopsies without rejection. Regarding TIRC7 mRNA in PBMC, transplant recipients showed lower levels than healthy individuals and, in contrast to the results obtained in biopsies, the levels were lower during rejection than in rejection-free periods. In summary, TIRC7 mRNA expression levels increase in biopsies and decrease in peripheral blood during acute cardiac rejection. We conclude that intragraft detection of TIRC7 transcripts is a useful tool not only for the diagnosis but also for the prediction of acute heart allograft rejection episodes.