Four episodes of early graft rejection have occurred in three patients following cardiac transplantation. In each, electrocardiographic abnormalities preceded the onset of overt cardiac failure. These included diminished voltage, right axis deviation, atrial arrhythmias, and first-degree heart block progressing to nodal rhythm. Vectorcardiograms showed decreased total spatial magnitude with rejection. Early clinical changes included fatigue, low exercise tolerance, tachycardia, and diastolic gallop rhythm. With overt cardiac failure, signs of low cardiac output developed followed by systemic venous congestion. Two patients were treated successfully with dactinomycin, high intravenous doses of methylprednisolone, and heparin sodium. The third died of pneumonia following therapy. Our experience to date supports the ECG as the most sensitive and reliable monitor of cardiac rejection. Clinical and physiological observations suggest myocardial restriction as the primary functional lesion in rejecting heart transplants.