Fine-needle aspiration biopsy (FNAB) is a routine diagnostic tool used for the monitoring of the graft during the first postoperative weeks after liver transplantation. The cellular pattern of acute liver rejection is typical in transplant aspiration cytology (TAC), documented and published by several authors. The lymphoid response associated with various viral infections may, however, provide differential diagnostic problems in the cytological monitoring. In this study, we have investigated in detail the cellular pattern of lymphoid response associated with hepatitis C virus (HCV) reactivation, and compared it with the pattern of cytomegalovirus (CMV) infection and with the typical diagnostic findings of acute cellular rejection. HCV reactivation was associated with rather mild total inflammation in the graft (4.5 +/- 1.5 CIU at the peak). The inflammatory infiltrate consisted mainly of small lymphocytes (3.1 +/- 0.2 CIU at the peak), with only occasional activated cells and without lymphoid blast response. No lymphoid activation was seen in the blood. CMV infection was associated with a mild immune response (3.9 +/- 0.4 CIU at the peak) recorded as a slight lymphoid activation and occasional blast cells both in blood and in the graft together with lymphocytosis in the graft (2.4 +/- 0.7 CIU at the peak). The typical findings of acute rejection were easily distinguished from the cellular pictures of both viral infections. The rejections were lymphoid blast (3.6 +/- 3.4 CIU at the peak) and activated lymphocyte (3.5 +/- 2.6 at the peak), dominated by a high peak of total inflammation (9.3 +/- 7.0 CIU). No blast cells and only a few activated cells were seen in the blood during rejection episodes. Thus, the cellular patterns of HCV reactivation and CMV infection differed slightly from each other, but significantly from that of acute liver allograft rejection monitored with the FNAB cytology.