T he history of medicine is replete with exam-ples of stout resistance to change. The lag time between development of new knowledge and its reduction to practice is directly proportional to that resistance. Sometimes this built-in conservatism of the system is good as, for example, in the case of the resistance to the approval of thalidomide for use in theUnited States. In other situations, however, conservatism may cost lives by delaying the transfer to practice of interventions that could be life saving. My thesis is that there was such a delay in recognizing the importance of hypercholesterolemia and its management. Why did it take so long for the causative role of hypercholes-terolemia in atherosclerosis to become generally accepted by the medical profession? Certainly it was a topic deserving of our closest attention, since for many years close to 50% of the deaths in the United States have been attributable to atheroscle-rosis and its complications. Yet there continued to be a great deal of resistance well after the cause-and-effect relation should have been evident. Even before clinical intervention studies provided the conclusive evidence, the cause-and-effect relation should have been easily read from the wealth of evidence at the biochemical, pathologic, epidemio-logic, and clinical levels. But it was not. It is my hope that by examining closely this particular" case history," we can gain insights that will be useful as we go on to try to understand and control other chronic diseases. Chronic diseases are much more difficult to deal with than acute diseases. It is more difficult to establish causal relations unambig-uously; it is more time consuming and expensive to prove efficacy of treatment. Perhaps there are some general lessons to be learned from a case history of