The morphologic and histologic examination of over fifty-five foci of metaphyseal/epiphyseal osteomyelitis and eleven septic joints from five cases of neonatal osteomyelitis and joint sepsis are described in detail. The severity of the bone and joint involvement varied considerably, allowing a better understanding of the pathophysiologic sequence of events in the disease in the neonatal time period. Of particular importance were (1) the multifocal nature of the disease, (2) the highly variable destruction of the growth plate (physis) by several discrete mechanisms, and (3) the invasion of the chondroepiphysis through the cartilage canal systems. Two of the cases died from respiratory complications several months following presumed successful treatment of their skeletal infections. S&pecimens showed significant growth plate damage continuing beyond the neonatal period. These findings support the need for rapid diagnosis and drainage, whenever feasible, to prevent long-term skeletal growth damage. The severity of involvement also should emphasize that this disease, especially in the neonate, is not an innocuous condition, as a recent review suggested.