Rabbits were given a diet containing 1% (w/w) cholesterol for 7 weeks to initiate atherosclerosis and then transferred to a low-cholesterol diet (regression diet) with or without 0.5% (w/w) cyclandelate for 10 weeks. In those fed regression diet alone aortic atherosclerosis increased significantly. Cyclandelate treatment decreased the extent and severity of aortic atherosclerosis. Thus in rabbits receiving cyclandelate the total cholesterol and calcium content of aorta was decreased by 45% and 69% of control values, respectively. The effects of cyclandelate occurred without significant lowering of serum cholesterol or alteration of cholesterol content of liver or calcium content of serum, liver or muscle. The result suggests a specific action of cyclandelate on atheromatous accumulations of the aortic wall.