The present study investigated gene expression of costimulatory molecule CD27 in relation to the occurrence of acute cardiac rejection. CD27 transcripts were measured by means of quantitative competitive reverse transcriptase-polymerase chain reaction in 120 endomyocardial biopsies and in 89 samples of blood mononuclear cells from 31 recipients. Higher levels of CD27 transcripts were observed in biopsies with rejection than in samples without rejection (medians, 7.1 and 1.9; P = 0.06). In contrast, blood mononuclear cells collected during rejection showed lower levels than blood mononuclear cells from rejection-free periods (medians, 3.3 vs. 7.9; P = 0.03). Considering only endomyocardial biopsies without rejection, the values were lower in samples from recipients who did not present any rejection during the first 6 months after transplantation than in those from recipients who had at least one rejection during the same period (medians, 0 vs. 3.5, P < 0.001; percentage of biopsies expressing CD27, 44% vs. 77%). In conclusion, the presence of intragraft CD27 mRNA may identify recipients at risk for developing acute rejection.