Heart transplantation is a therapeutic alternative for selected patients with refractory heart failure. Acute allograft rejection is one of the main causes of early death after transplantation. The cellular rejection is characterized by cellular infiltrates with or without myocyte necrosis. However, some patients develop left ventricular dysfunction due to rejection without evidence of cellular infiltration. In these patients, the rejection is mediated by antibodies and complement. Humoral rejection is a relative rare but potentially fatal form of acute allograft rejection. We report two patients with left ventricular dysfunction secondary to humoral rejection, shortly after cardiac transplantation. Both patients were treated with methylprednisolone, and azathioprine was substituted by cyclophosphamide. One patient underwent plasmapheresis. The clinical outcome was satisfactory and the left ventricular function returned to normal in both cases. The diagnostic and therapeutic strategies for the management of humoral rejection are reviewed.