The lipid composition of the red cell membrane and plasma was investigated in a patient with hypothyroidism, in whom an acquired hemolytic anemia was reversed after thyroid hormone replacement therapy. Before therapy, most of the plasma lipids were elevated. In the red cell membrane, phosphatidylcholine (PC) and free cholesterol (FC) were increased, and the free cholesterol to phospholipid (FC/PL) ratio was elevated. Erythrocyte sodium transport was also increased, while intracellular sodium and potassium concentrations were normal. After therapy, the derangement of lipid levels and sodium transport activity were normalized with improvement of the hemolytic anemia. The shape of peripheral red cells also returned to normal after treatment. These findings suggest that the derangement of the red cell membrane lipids and plasma lipids derived from hypothyroidism can be a major cause of hemolysis in this patient.