A model for biological membranes is proposed according to which the plasma membrane consists of two functionally different polar-nonpolar-polar leaflets separated by a polar space. The binding of watersoluble proteins, integral lipoproteins and spanning proteins to a biological membrane as well as possible Conformations of interphase peptides partitioned between polar and nonpolar layers are discussed. A model for the diffusion of water soluble proteins across adenylate kinase (5), NDP kinase (2), ATPase (3, 43), and protein kinase (6, 44). Phenomena such as ghost resealing ( c $ :26), secretion of proteins apparently without exocytosis (23,32), and the transport of polynucleotides across intact plasma membranes (cf.: 36)are difficult to explain with the traditional lipid bilayer concept of a plasma membrane. This concept for biological membranes in general has previously been questioned nonpolar layers Of a membrane is described. Three complete biological membranes containing two leaflets and an inter-leaflet space are defined. These are: 1:The inner nuclear membrane + the perinuclear space and the endoplasmatic cisternae + the outer nuclear membrane and the endoplasmatic reticulum, 2: the inner mitochondrial membrane + the mitochondrial intermembraneous space + the outer mitochondrial membrane and 3: the cytoplasmic leaflet of the plasma membrane + an intramembraneous space in the plasma membrane + the outer leaflet of the plasma membrane.on morphological (43, chemical (28) and biofunctional (28) grounds. Perhaps the most convincing objection is that lipids can be extracted from Some biological membranes without altering the usual trilaminar appearance in electronmicroscopic pictures (18). Also the nature of the material in the sheet which does not st& with osmium remains undetermined because according to the traditional view strong hydrophobic bonds would be expected to be present thus preventing, for example, tangential splitting of this region on freeze-etching (6: 51).