The endoneurium of the mouse sciatic nerve was studied by scanning and transmission electron microscopy to elucidate their three-dimensional architecture. The endoneurium consisted of collagen fibrils, and occasional fibroblasts and blood vessels. Collagen fibrils surrounded individual nerve fibers, forming two distinct layers of connective tissue sheath: the outer one was composed of bundles of longitudinally oriented collagen fibrils and the inner one was of a delicate network of interwoven thin collagen fibrils. These outer and inner layers of collagen fibrils correspond to the two fibrous sheaths known as the sheath of Key and Retzius and the sheath of Plenk and Laidlaw, respectively, revealed on nerve fibers by silver impregnation. Some of the finest collagen fibrils forming the inner network are closely attached to the basal lamina of Schwann cells, suggesting that these fibrils are concerned with the connection between the basal lamina and the inner collagen network. These two layers of collagen fibrils were found on all the nerve fibers, suggesting that they represent a general structure ensheathing the peripheral nerve fibers. Although these layers occur also on unmyelinated nerves, they are most developed on the largest myelinated fibers.