SUMMARY1. The aim of the study was to examine the effect of the angiotensin‐converting enzyme inhibitor perindopril on the development of atheroma in the cholesterol‐fed rabbit.2. The normal human carotid artery, like most large human arteries, has a preformed diffuse intimal thickening. To model this thickening, the right carotid artery of the 12‐week‐old rabbit had an expanded balloon catheter passed down it to remove the endothelium and partially damage the media.3. Fourteen weeks after this operation, a myointimal thickening similar in almost all respects to the human intimal thickening had developed. The rabbits were then divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a 1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); (iii) a 1% cholesterol diet plus a non‐hypotensive dose of perindopril (0.01 mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non‐hypotensive dose of perindopril (0.01 mg/kg per day).4. After 6 weeks of treatment the animals were sacrificed. There were ameliorating effects of both hypotensive and non‐hypotensive doses of perindopril on the development of plaques, as determined by the area of intima covered by Oil Red‐O‐staining plaque and light microscopy.5. Cell culture studies indicated that perindopril has no effect on smooth muscle proliferation, but increases collagen and non‐collagen synthesis by smooth muscle cells and decreases their binding of the atherogenic lipoprotein beta‐very low density lipoprotein (β‐VLDL).6. The results suggest that perindopril has a beneficial effect in decreasing the severity of atherosclerotic lesions in the cholesterol‐fed rabbit, possibly by affect