This paper reports the first ultrastructural study of the thoracic aorta and dermis of an 18-month-old boy with Menkes' syndrome who had been treated in the year prior to death with intravenous copper. Light microscopy revealed absence of distinct elastic laminae in the inner third of the media, but irregular clumps of elastin were present. In the middle and outer media the elastic laminae were fragmented and discontinuous. The few cells present in the media were irregular in shape and, unlike normal smooth muscle cells, were seen to contain large accumulations of metachromatic material. A large amount of collagen was present throughout the aortic wall. Ultrastructurally, the elastin present was electron dense and surrounded by a prominent sheath of microfibrils approximately 110 Å in diameter. Similar observations were made for skin elastic fibers. The cells of the middle and outer thirds of the aortic wall contained myofilaments displaced peripherally by large aggregates of a flocculent material. These aggregates were largely nonmembrane limited and may represent an intracellular cytoplasmic accumulation of proteoglycan. Skin fibroblasts did not contain such aggregates. The abnormal elastic fibers observed in this child can be explained on the basis of a copper deficiency occurring very early in development, perhaps even in utero. The abnormally large amount of collagen present throughout the aortic wall and the sparse cell population with large cytoplasmic accumulations of metachromatic material are features not previously described. The collagen probably indicates a generalized repair response and may in part account for the sparse cell numbers because of its abundance. However, the nature of the large intracellular aggregates and their relationship to copper deficiency remain uncertain.