Acute rejection is the end result of progressive accumulation (most prominently in portal tracts) of mononuclear cells, PMNs, and eosinophils. The anatomic location of these cells, such as outside the limiting plate, in the venous endothelium or biliary epithelium, appears to change with the development of acute rejection. Although neither the density of the mononuclear cell infiltrate nor the total number of mononuclear cells and PMNs appear to correlate closely with the syndrome of acute rejection, spillout from the portal tracts and the number of eosinophils are reliable predictors of acute rejection in our population of patients. Acute rejection is a syndrome and liver dysfunction is an essential part of the diagnosis. The transient appearance of portal tract pathologic changes consistent with acute rejection occurs without hepatic dysfunction in approximately 10 to 20% of patients. Although the nature of this apparently innocent phenomenon is not understood, resolution occurs without antirejection therapy. Because of the complexity of liver transplantation care, and the need to minimize immunosuppression, serial biopsy continues to supply dynamic information needed for allograft monitoring. We propose that the data safely obtained from these biopsies can guide immunosuppression therapy.