Apoptosis mediated by the Fas/Fas ligand (FasL) has been implicated in rejection of solid organ allografts and it has been recently proposed that soluble forms of Fas could interfere with this interaction, blocking apoptosis. The purpose of this study was to analyze intragraft Fas, FasL, and soluble Fas mRNA levels in relation to acute rejection in cardiac allografts in humans. mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction in 42 samples of endomyocardial biopsies obtained from 18 cardiac transplant recipients within the first 6 months after transplantation. FasL and Fas mRNA levels were higher in biopsies with rejection than in biopsies without rejection, and no difference was observed in soluble Fas mRNA. During rejection, there was a positive correlation between the mRNA levels of Fas-FasL, Fas-soluble Fas, and FasL-soluble Fas. During quiescent periods, however, the only correlation observed was between Fas and soluble Fas mRNA levels. In conclusion, our findings do not suggest a role for soluble Fas, confirm the heightened expression of FasL, and indicate, for the first time, an increased expression of Fas in acute rejection of cardiac allografts.