Numerous observational and intervention studies have shown that total (and LDL) cholesterol levels correlate positively with progression of atherosclerosis. It has also been shown that a mean low HDL cholesterol level is a potent predictor of CHD (coronary heart disease) in populations in which atherosclerotic diseases are prevalent. Recently, studies based on repeat angiographic examination, which are reviewed here, have shed new insight on the different roles that total cholesterol (or LDL) and HDL-cholesterol play on progression and regression of coronary atherosclerosis, respectively. From an epidemiological viewpoint, based on observational as well as intervention studies, the theory emerges that progression correlates best with total (and LDL-) cholesterol and that regression correlates best with HDL-cholesterol. The working hypothesis, if confirmed, will have practical implications for primary and secondary preventive measures.