Venous grafts implanted in the systemic circulation progressively undergo wall thickening, a phenomenon thought to be responsible for late saphenous graft disease after bypass surgery. Angiotensin converting enzyme (ACE) inhibitors recently have been shown to prevent myointimal thickening after arterial injury. Thus, the goal of the present study was to test the effects of ACE inhibition in a rat model of venous graft. For this purpose, a segment of jugular vein was interposed in the right carotid artery of normotensive rats that received either placebo or 10 mg/kg/day cilazapril, a long-acting ACE inhibitor. Three weeks later, the venous grafts and the implanted carotid arteries were fixed under perfusion and embedded for morphometric analysis. In the control group, the wall of the venous graft thickened dramatically compared with the nonimplanted contralateral jugular vein (up to 20 times increase in total cross-sectional area). On the arterial side, thickening of the wall and a neointima also were observed, most likely because of the surgical arterial injury. Cilazapril decreased by 33% (p less than 0.05) and 26% (p less than 0.01) the total cross-sectional area of the wall of the venous grafts and of the carotid arteries, respectively. Thus, these results suggest a role of the renin-angiotensin system in the early process of venous graft thickening. This study also suggests that ACE inhibitors could be a new therapeutic means to prevent late saphenous graft disease.