The histopathologic indication for starting antirejection therapy has so far been given by the diagnosis of moderate rejection in endomyocardial biopsies, that is, rejection with necroses of myocytes and predominantly lymphocytic infiltrates (corresponding to the descriptive diagnosis of moderate rejection in the Stanford classification, grade 4 and more in the Texas classification, and A-3 moderate rejection in the Hannover classification). Our present results, however, have shown that the critical limit for the onset of antirejection therapy may be fixed somewhat higher on the scale of severity of acute rejection and that it may be reasonable to define an affection of more than 20% of the total biopsy material by morphologic changes corresponding to the traditional definition of moderate acute rejection as the decisive histopathologic finding that should induce antirejection therapy. This means that the diagnosis of moderate rejection has to be divided into two groups: (1) A-3a moderate acute rejection not yet requiring therapy that, however, does necessitate bioptic control within 7 to 10 days; (2) A-3b moderate acute rejection requiring antirejection therapy. The introduction of this differentiation of histopathologic diagnoses is not just another sophisticated scientific theorem; its practical significance may be seen in a definitive restriction of the application of antirejection therapy, which means a reduction of the risks and side effects imposed on heart-transplanted patients by chemotherapy and particularly by steroid therapy.