Recent studies suggest that the primary action of insulin is on the permeability of cell membranes. This idea may account for the effects of the hormone in broken cell preparations as well as in tissue preparations with intact cells if the concept of the cell membrane is broadened to include endoplasmic reticular extensions and the membranes of subcellular organelles. Following on the initial demonstration that insulin was bound to muscle and the elucidation of the structure of insulin, evidence was presented that this binding involves a sulfur-sulfur linkage between hormone and target tissue. In the present work, skeletal muscle cell ghosts were prepared for use in studying the chemical nature of the attachment of insulin to a relatively pure cell membrane preparation.