Four classes of etiologic agents that cause human illness have been discovered. Sometimes members of two or more classes of agents cooperate to cause illness. Knowledge of etiology is necessary if a disease is to be eradicated. The leading causes of death in the United States have changed dramatically in the last century. Infection has been replaced by chronic illnesses of obscure etiology. Ischemic heart disease is the leading cause of death in middle age and is the major obstacle to becoming old. There are numerous similarities between animals deficient in copper and people with ischemic heart disease. The most important of these similarities are glucose intolerance, hypercholesterolemia, abnormal electrocardiogram, hyperuricemia, and hypertension, as these characteristics are predictive of risk of ischemic heart disease. No other nutritional insult has produced these characteristics in experiments with animals; men fed diets low in copper have been found to have increased cholesterol, decreased glucose tolerance, and abnormal electrocardiograms. The process that results in ischemic heart disease is remarkably similar to that of copper deficiency. Links have been found between copper metabolism and several hypotheses on the origin of ischemic heart disease. Several aspects of the lipid hypothesis can be interpreted in terms of copper metabolism. More features of the etiology, pathogenesis, and pathophysiology of ischemic heart disease can be explained in terms of copper deficiency than can be explained by any other environmental insult.