A model of arterial graft arteriosclerosis is described in which arterial wall immune injury was induced by grafting segments of abdominal aorta between two histologically incompatible strains of rats. The effect of hypertension and its treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril was tested using inbred spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto [WKY]). Each of the grafted hypertensive and normotensive rats was randomly allocated to placebo treatment (10 SHR, 10 WKY) and perindopril treatment (2 mg/kg/day) (10 SHR, 10 WKY). The immune injury and the arterial wall response were quantified morphometrically 2 months after the grafting using specific stains for collagen, elastin, and nuclei. Hypertension was associated with a significant increase in intimal thickness. Treatment with perindopril greatly reduced intimal proliferation, decreasing the intimal thickness and the collagen content within the intimal layer. In contrast, hypertension and ACE inhibition had little effect on the arterial wall injury. We conclude that hypertension and its treatment with perindopril significantly affect graft arteriosclerosis. These effects seem to be independent of their effects on arterial wall injury, but not independent of blood pressure.