Histological analysis of endomyocardial biopsies (EMB) is regarded as the most satisfactory technique for monitoring crisis of rejection in heart transplanted patients. In this study, 42 biopsies from 14 patients who underwent heart transplantation were examined. Three patients did not present any rejection crisis at the date of the biopsy analysis, six were examined during an early rejection crisis (day 7-70 post-graft), and five were examined during a late rejection crisis (day 74-960 post-graft). Since granzyme B and perforin are proteins associated with cell lysis histological grading and cell phenotype analysis, in situ hybridization using granzyme B and perforin [35S]RNA probes was performed on 30 EMB to characterize the cytolytic activation of heart infiltrating cells. Our data suggest that granzyme B and perforin could be used as predictive markers for acute rejection in patients with early rejection crisis. Their detection might be an indication to administrate corticoids to resolve an acute rejection crisis. In contrast, their absence in patients with late rejection crisis appears as a good prognostic factor for the outcome of rejection and raises the question of the necessity to treat such patients with additional corticoid treatment.