INTIMAL PROLIFERATION IS thought to be initiated by the migration and proliferation of smooth muscle cells after endothelial damage. These changes may be induced, in part, by mitogenic growth factors such as insulin-like growth factor-1 (IGF-1). This study was designed to investigate the role of locally synthesized IGF-1 and its receptor in the arterial wall in response to the exposure to periarterial blood. Rat femoral arteries were exposed to periarterial blood for various time periods (control, 1, 3, 7, 14, and 21 d). Total ribonucleic acid was extracted from the arteries of 10 to 15 animals, and the expression of IGF-1 messenger ribonucleic acid in treated and untreated arteries was analyzed using dot blot analysis. To identify and localize IGF-1 receptors on the arterial walls, an in situ ligand binding of IGF-1 to the arterial sections was utilized using [125I]IGF-1 as a tracer. Our results revealed that luminal narrowing was maximum at 7 days posttreatment. Intimal proliferation occurred at 14 and 21 days. The results of dot blot analysis showed that the expression of IGF-1 messenger ribonucleic acid was increased four-fold by Day 3 and remained elevated up to 7 days, then gradually decreased. In situ [125I]IGF-1 binding to the normal rat femoral artery localized IGF-1 receptors to the arterial wall. There was a marked increase in the number of receptors at 3 and 7 days after treatment with periarterial blood. These results suggest that locally synthesized IGF-1 and its receptor may function in an autocrine and/or paracrine loop as part of the response of the arterial wall to periarterial blood, resulting in intimal proliferation.