Injury of an artery by passage of a balloon catheter causes both endothelial denudation and medial damage and produces a marked smooth muscle cell (SMC) proliferative response. In this study, the endothelium from rat carotid arteries was removed by use of a rotating loop of 5/0 monofilament suture (gentle denudation technique), which did not cause any detectable damage to the underlying medial cells but did cause platelet adherence. Expression of platelet-derived growth factor (PDGF) A-chain and PDGF receptor mRNA was comparable to that seen in ballooned carotids, but the medial SMC proliferative response to gentle denudation was markedly reduced when compared to that observed after balloon denudation (1.4% vs. 13.6%). Intimal lesions were only observed in those zones that remained denuded for more than 7 days. These results demonstrate that a denuding injury with no medial trauma is sufficient to induce intimal lesions and that the significantly higher proliferation seen in ballooned vessels might reflect a response of the medial cells to trauma that occurred during denudation.