Ultrasound has become a well-established method for the clinical evaluation of carotid artery atherosclerosis. In the past few years, high-resolution ultrasound methods have been used more frequently in the study of the natural history of atherosclerosis. Most recently, B-mode ultrasound has enabled investigators to detect and monitor early stages of carotid artery atherosclerosis, when lumen stenosis is between 15 and 45%. Epidemiological studies using high-resolution ultrasonography will allow researchers to correlate traditional risk factors for atherosclerosis with changes over time in lesion incidence, prevalence, and severity. Investigators can also study the effects of drug treatment on the early stages of disease by monitoring rates of lesion progression or regression in carotid arteries. Several large epidemiological and clinical intervention trials are currently underway that use high-resolution B-mode ultrasonography to measure intima-media or total wall thicknesses in extracranial carotid arteries. In these studies, the reproducibility of arterial wall measurements is the most critical factor in establishing rates of lesion progression or regression. This paper describes the ultrasound methods currently being used to determine the effect of the calcium antagonist, isradipine, on patients with asymptomatic carotid artery atherosclerosis.