Abstract The contributions of serum lipoproteins and splenic conditioning to the genesis and destruction of spur red cells were studied in 20 patients with severe liver disease, one of whom underwent splenectomy. The cholesterol-phospholipid ratio of serum low-density lipoproteins correlated with that of spur-cell membranes, and a general relation existed between the magnitude of this abnormality of lipid composition and severity of anemia. Splenectomy did not influence the abnormality; however, it prevented loss of cell-surface area and remodeling of cell architecture, which spur cells otherwise undergo in vivo, and decreased the hemolytic rate. The spur-cell phenomenon appears to be a two-phase process. The first (lipid) phase is characterized by acquisition of cholesterol, surface area and a scalloped cell contour, and it is dependent on serum lipoproteins. The second (conditioning) phase is characterized by a loss of cell-surface area, transformation to a spiculated cell contour and hemolysis, and i...