The implications of a double polar-nonpolar-polar leaflet construction of the plasma membrane are investigated. Experimental data from transmission electron microscopic and enzymologic characterization of plasma membranes are advantageously interpreted in these terms compared to interpretation in terms of lipid bilayer. X-ray diffraction and electron spin resonance studies do not differentiate between the present and previous models for the structure of plasma membranes but electron spin resonance data that fail to indicate a statistical distribution of spin labels also fail to support the fluid mosaic model for cell membranes. Results from experiments involving vectorial digestion and labelling of plasma membranes as well as freeze fracture electron microscopic data are compatible with the present model. The molecular composition of the human erythrocyte membrane is investigated whereby the band 111 protein and glycophorin are suggested to be the structural proteins of the outer leaflet and the spectrins those of the inner leaflet.