Percutaneous transluminal angioplasty has received considerable attention in the treatment of obstructive atherosclerotic lesions in humans. However, restenosis frequently occurs and has limited the long-term effectiveness of this procedure. To study restenosis, a model of atherosclerosis was developed in 16 New Zealand rabbits. Atherosclerosis was induced in one or both iliac vessels by balloon deendothelialization followed by a 2% cholesterol diet for 6 weeks. Angiographic lesions were demonstrable in all animals. Fourteen iliac vessels served as controls, and nine underwent successful angioplasty with an increase in luminal diameter from 1.0 +/- 0.2 to 1.9 +/- 0.4 mm (p less than 0.01). After 4 weeks on a high cholesterol diet, all animals had another angiogram, which documented significant progression of disease in only six of 14 control iliac vessels, but in all nine dilated vessels. The average decrease in luminal diameter was 0.2 +/- 0.3 mm for the control group compared with 1.6 +/- 0.5 mm for the dilated group (p less than 0.01). Histopathological correlates revealed further remodeling of at various stages of organization and recanalization. In summary, this study demonstrates that restenosis occurs following transluminal angioplasty and is significantly more frequent than the natural progression of disease in a rabbit model of atherosclerosis. The mechanism of this restenosis appears to be related to intraluminal thrombosis and acceleration of atherosclerosis. Evaluation of antiplatelet drugs in the prevention of restenosis seems warranted.