High blood pressure (BP) is associated with increased risk of vascular disease, including myocardial infarction and stroke. Since drugs that lower BP will reduce the risk of those complications of hypertension that are due to high pressure (strokes due to small-vessel disease, including lacunar infarction and intracerebral hemorrhage due to rupture of microaneurysms, heart failure, and renal failure), it has been assumed that such drugs would also reduce the risk of myocardial infarction due to atherosclerosis. However, in addition to hypertension, many other factors are involved in the atherosclerotic process including blood lipids such as cholesterol, blood platelets, and arterial flow disturbances such as turbulence and vortex formation. Some drugs that lower BP have unwanted effects on blood lipids and arterial flow patterns, which are thought to offset the benefit of BP reduction, whereas other drugs have beneficial effects on such factors. Ames has calculated that the adverse effects of antihypertensive drugs on lipids are enough to completely offset the benefit of treating mild hypertension. We have shown that antihypertensive drugs have different effects on blood velocity, and that these effects are associated with differences in the effects of drugs on arterial flow disturbances at the site of carotid stenosis in man, such that propranolol reduced, and hydralazine increased, the occurrence of abnormal high-velocity flow patterns associated with turbulence and vortex formation. In cholesterol-fed hypertensive rabbits (one-kidney Goldblatt), propranolol was more effective than hydralazine in preventing the occurrence of aortic atherosclerosis, even though hydralazine lowered blood pressure more effectively.(ABSTRACT TRUNCATED AT 250 WORDS)