The red cell membrane contains approximately equal amounts of lipids and proteins. Membrane lipids are either phospholipids or neutral lipids, mostly unesterified cholesterol. Membrane phospholipids are asymmetrically arranged into a lipid bilayer two molecules thick. Choline phospholipids are more abundant in the extracellular surface whereas amino phospholipids are more concentrated on the inner leaflet of the bilayer. Cholesterol is intercalated between the phospholipid molecules. The relative amounts of cholesterol and phospholipids are responsible for the fluid properties of the erythrocyte membrane. Alterations in the membrane cholesterol-phospholipid ratio result in morphologically abnormal erythrocytes with decreased life span. Membrane proteins are also asymmetrically oriented within the lipid bilayer and can be divided into three functional sets: structural, catalytic and receptor proteins. Sprectrin and actin are the two main structural proteins that together form a submembranous cytoskeletal meshwork that is responsible for the viscoelastic properties of the erythrocyte membrane. Band 3, or the anion channel, is a major transmembranous protein involved in the transport of water and anions and is a carrier of the blood-group-I antigen. Glycophorin A, a sialic-acid-rich glycoprotein, is the major contact or receptor membrane polypeptide that also spans the lipid bilayer. The MN blood group determinants and possibly other biologic receptor sites have been localized on the extracellular portion of glycophorin A. At least 35 to 40 enzymes are confined to the membrane and, undoubtedly, play a vital role in the maintenance of normal structure and function of the erythrocyte.