Because anemic persons have lower cholesterol and whole blood viscosity than those who are not anemic, we hypothesized that subjects with hereditary spherocytosis who have not had the spleen removed should have fewer arteriosclerotic events than unaffected family members. We defined arteriosclerotic events as myocardial infarct, stroke, coronary artery surgery, and carotid artery surgery. We compared the rate of these events in affected-not splenectomized persons to the rate in unaffected family members. The relative risk of an arteriosclerotic event in hereditary spherocytosis patients with a spleen was one fifth that in unaffected family members. These data support the hypothesis that chronic anemia retards the development of arteriosclerosis. Spherocytosis is another example of an inherited condition that conveys an advantage in one system and a disadvantage in another.