Histologic evidence of restenosis after percutaneous transluminal coronary angioplasty has been confined to the site of previous dilation. In this study, attention is focused on the accelerated development of coronary stenosis proximal to the site of previous angioplasty in a necropsy patient who developed severe left main stenosis 4 months after successful dilation of the proximal left anterior descending coronary artery. The unique fibrocellular tissue proliferation at the site of previous angioplasty and involvement of the adjacent distal segment of the left main coronary artery make possible the histologic diagnosis of accelerated left main coronary artery narrowing. Mechanisms for development of coronary stenoses proximal to the angioplasty site include: intimal injury by guiding catheters, guide wires, dilating balloons or combinations; or retrograde extension of the fibrocellular response to an adjacent proximal coronary segment. Histologic analysis of left main coronary arteries from 11 patients who died within 72 hours of angioplasty of the left coronary system disclosed focal loss of luminal endothelium in 9. This finding suggests that intimal injury from catheters or balloons, or both, proximal to the angioplasty site probably initiates a fibrocellular reaction. The amount of underlying atherosclerotic plaque in the injured proximal coronary segment determines the clinical significance of a subsequent fibrocellular response.