Atherosclerosis, the process underlying coronary heart disease, peripheral vascular disease, and stroke, begins in childhood and progresses through several stages to result in clinically manifest disease in middle age and later. Elevated plasma low-density lipoprotein cholesterol levels, lowered high-density lipoprotein cholesterol levels, and elevated blood pressure are associated with more extensive and more severe atherosclerosis and also with greater risk of clinical disease. Cigarette smoking is firmly established as a risk factor for coronary heart disease and peripheral vascular disease. It is associated with more severe coronary atherosclerosis, but not enough to account for the twofold or greater risk of coronary heart disease among smokers. Smoking is associated with much more severe atherosclerosis of the abdominal aorta, which is consistent with the much greater risk of aortic aneurysm and peripheral vascular disease among smokers. Smoking induces a wide variety of physiologic responses, some of which appear likely to be involved in accelerating atherogenesis or increasing the probability of thrombosis. These responses include reduction in plasma high-density lipoprotein cholesterol concentration, elevation in plasma fibrinogen concentration, and elevation in white blood cell count. The rapid amelioration of the risk of cardiovascular disease after cessation of smoking suggests that these processes are readily reversible.