Intimal smooth muscle (SMC) proliferation was examined in the rat left carotid in regions lacking endothelium for prolonged periods of time. Arteries of animals injected with tritiated thymidine and Evans blue were examined at intervals between 0 and 12 weeks. The endothelial layer was regenerated from the ends of the denuded segment but failed to cover the central third of the artery by 12 weeks. Autoradiography on samples from this central region (stained blue) and the endothelialized ends (white) showed that SMC proliferation reached a maximum at 48 hours in the media (46%) and at 96 hours in the intima (73%). Subsequently, the thymidine index declined to baseline (0.06%) by 4 weeks throughout the media and by 8 weeks in the intima covered by endothelium. SMC proliferation persisted at a high level (3.8%) at the surface of the intima lacking endothelium even at 12 weeks. Despite continued proliferation of luminal SMC, total arterial SMC number was the same at 2 and 12 weeks. These results support the concept that intimal SMC proliferation after arterial injury is an acute event related to the initial injury process. Persistent proliferation of luminal SMC does not result in an increase in intimal cell number.