According to the International Society for Heart and Lung Transplantation, a single focus of lymphocytic infiltration associated with myocyte injury in a cardiac allograft endomyocardial biopsy is focal moderate cellular rejection (Grade 2). We reviewed 115 endomyocardial biopsy specimens that were completely negative (n = 17), had a Quilty A (n = 17) or Quilty B (n = 46) lesion, or had a lesion fulfilling the criteria of grade 2 rejection (n = 35). By studying step sections (mean = 18) or sections stained for elastic tissue and collagen, we showed continuity of the focus of grade 2 rejection with the endocardium in 32 of 35 cases; these results justify reclassification of these foci as Quilty B lesions, which are defined as endocardial infiltrates that encroach on the underlying myocardium and that may be associated with myocyte injury but are not generally considered to represent acute rejection. Immunohistochemical staining for T and B lymphocytes and histiocytes showed similar patterns in deeper zones of Quilty B lesions and lesions initially regarded as grade 2 rejection. Normal hemodynamics were observed with 16 of 17 completely negative biopsy specimens, 16 of 17 Quilty A biopsy specimens, 46 of 46 Quilty B biopsy specimens, and 35 of 35 grade 2 rejection biopsy specimens. No grade 2 rejection was treated; only 1 biopsy specimen progressed to grade 3A rejection in a subsequent biopsy 2 months later. Most, if not all, cases of grade 2 cellular rejection can be shown to be Quilty B lesions, are not associated with hemodynamic abnormalities, and do not require augmented immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)