A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.