The role of secretion of proteins for the attachment of ribosomes to membranes has been well established. That another function must exist for membrane-ribosome interaction is suggested by observations on: (a) the active synthesis of proteins on membrane-bound ribosomes of predominantly non-protein secreting cells, and b) the massive proliferation of membrane-bound ribosomes during active growth and development of both secretory and non-secretory tissues. Literature on functional and compositional differences between membrane-bound and free ribosomes is reviewed and it is proposed that a major function of ribosome-membrane interaction is to effect a topological segregation of different populations of ribosomes synthesizing different classes of proteins.