The purpose of this study was to analyze apoptosis in the vessel wall after stent implantation in the canine portal vein and also to investigate the expression of the p21 cyclin-dependent kinase inhibitor, which may regulate cellular proliferation after vascular injury. Uninjured, control veins had few detectable TUNEL-positive cells in the intima and media (0.829 +/- 0.413%). At 4 weeks after stent implantation, TUNEL-positive cells significantly increased to 50.5 +/- 4.639%. These cells were predominantly located around the stent struts, and appeared to be smooth muscle cells morphologically. At 12 weeks, 44.7 +/- 6.178% of the intimal and medial cells were still TUNEL positive, and there was no significant difference between 4 and 12 weeks. P21 was not detected in uninjured, normal veins. At 4 and 12 weeks after stent implantation, positive p21 immunostaining was sparsely expressed in the intima and media adjacent to the stent struts. Thus, stent implantation induced a prolonged apoptotic response and increased expression of p21 in the portal venous system. This prolonged apoptotic response, possibly regulated by p21, may have a significant role in modulating the cellularity of intimal formation.