Purpose: The expression of c-MYC oncoprotein in proliferating smooth muscle cells (SMCs) was analyzed in an experimental model of vein graft intimal thickening. Methods: Superficial epigastric vein grafts were inserted into the femoral arteries of male Sprague-Dawley rats. The vein grafts were harvested at 0 hr, 2 days, 1 week, 2 weeks, and 4 weeks after grafting and were rapidly frozen in liquid nitrogen. Immunohistochemical labeling and morphologic analysis of vein graft sections with a double staining technique were used to identify c-MYC/alpha SMC actin and proliferating cell nuclear antigen (PC10)/alpha SMC actin within intimal cells. c-MYC/alpha SMC actin and PC10/alpha SMC actin positive cells were quantitated in the perianastomotic area (R-1) and the body of the graft (R-2) for each time period. Total wall and intimal thickness of perfusion fixed vein grafts were measured with a computer digitized system. Results: Intimal and total wall thickening in the R-1 region peaked at 1 week (27.4 and 579.4 μm, respectively) and were significantly thicker (P < 0.01) than the same region at 6 hr after graft implantation (6.0 and 113.5 μm, respectively). Staining for c-MYC and PC10 in R-1 was also significantly higher (P < 0.05) at 1 week (5.75 and 7.00 positive cells/10 cells, respectively) compared with that at 6 br (1.5 and 1.33, respectively). The R-1 region stabilized and remodeled over the following 3 weeks, while c-MYC and PC10 staining progressively decreased. In the R-2 region, intimal thickness significantly increased (P < 0.05) from 6 hr (4.0 μm) to 1 week (12.0 μm) and stabilized, while total wall thickness increased throughout the first week and the difference became significant at 2 weeks (P < 0.05). Staining for c-MYC and PC10 paralleled the staining in R-1 with a significant peak at 1 week (P < 0.05). Conclusions: c- MYC oncoprotein is expressed early after experimental vein grafting, with peak expression at 1 week. This occurs during a period of maximal intimal thickening, SMC proliferation, and increased expression of PC10. Expression of c-myc protooncogene may contribute to the induction and regulation of SMC proliferation, producing intimal hyperplasia.