Cardiovascular diseases are presently the leading causes of morbidity and mortality in Western societies, and early in the next millennium they are expected to become the main cause throughout the world. Atherosclerosis, a multifactorial process, is mainly responsible for these diseases, and genetic and environmental factors play significant roles in its development. More than a dozen genes, including those encoding apolipoproteins, enzymes of lipoprotein metabolism and receptors, affect the outcome of the process, but the list is far from complete. As well as environmental factors such as cigarette smoking or life-style, diet has an important role, because it is universal and essential for life. The human diet that best prevents atherosclerosis still needs to be defined and tested. The period of atherogenesis is lengthy in humans, and so it is practically impossible to study how different diets affect the process. All of these factors mean that dietary modifications must be tested on animal models with certain characteristics. The pathological process in these animal models should be similar to that in humans, but should develop over a shorter period, the genetics should be well defined and the progenies large, and the animals should be easy to handle and cheap to maintain. All of these criteria are met by apolipoprotein E knockout mice.