Biopsy specimens of the lateral aspect of the femoral head and neck were obtained from five children with Legg-Calve-Perthes disease and were studied using histochemistry and electron microscopy. Beneath the normal articular cartilage there was a thick zone of hyaline (epiphyseal) cartilage containing sharply demarcated areas of hypercellular and fibrillated cartilage with prominent blood vessels. The fibrillated cartilage was strongly positive to alcian blue, weakly positive to periodic acid-Schiff, and positive to aniline blue. The interterritorial matrix in the hypercellular areas was weakly positive to both alcian blue and periodic acid-Schiff. Ultrastructural examination of these areas revealed many irregularly oriented large collagen fibrils and variable amounts of proteoglycan granules. These results suggest that in the fibrillar areas there are: (1) a high proteoglycan content, (2) a decrease in structural glycoproteins, and (3) a different size of collagen fibrils from that of normal epiphyseal cartilage. The hypercellular areas had a decrease in proteoglycans, glycoproteins, and collagen. The lateral physeal margin was often irregular, with a marked reduction of collagen and proteoglycan granules, and contained numerous large lipid inclusions. CLINICAL RELEVANCE: The abnormal areas in the epiphyseal cartilage of patients with Legg-Calve-Perthes disease have different histochemical and structural properties from normal cartilage and from fibrocartilage. This suggests that the disease could be a localized expression of a generalized, transient disorder of epiphyseal cartilage that is responsible for delayed skeletal maturation. The cartilage lesions are similar to those seen in the vertebral plates in patients with juvenile kyphosis. Whether the epiphyseal cartilage abnormalities are primary or are secondary to ischemia remains uncertain; however, it appears that the collapse and necrosis of the femoral head could result from the breakdown and disorganization of the matrix of the epiphyseal cartilage, followed by abnormal ossification.