Osteomyelitis nearly always begins in the diaphysis of the long bones, usually near the epiphyseal line. This is an important point, clinically, because tuberculosis practically begins in the epiphysis. In rare cases, however, osteomyelitis begins in the epiphysis, and so may simulate tuberculosis. The femur and tibia are the bones most frequently attacked, but no bone is exempt. Usually only one bone is affected, but cases of multiple bone infections are not rare. The primary area of infection is always in the bone marrow. The bony trabeculae and the cortex are destroyed only secondarily. The process nearly always begins in the diaphysis, but then may extend into the epiphysis and produce suppuration of the joint. Once the organisms have gained access to the marrow, they produce a toxin which causes necrosis of the adjacent marrow cells, and this necrosis may extend over a very considerable portion of the bone before marked infiltration with leucocytes occurs. The infection usually extends quite early through the dense cortex by way of the Haversian canals, and produces an inflammatory exudation and suppuration between the periosteum and the outer layer of the cortex, which is designated _subperiosteal abscess_. Such an abscess may strip the periosteum from the bone over very extensive areas. The infection may then extend to the adjacent soft parts, muscles and subcutaneous tissue, and form an abscess outside the periosteum. If, from spontaneous opening of the abscess or from operation, a fatal result is avoided, the infective process may be limited and the process of repair may begin. As a rule, a portion of the infected marrow and cortex become completely necrotic, and the lime-bearing portion of the bone persists as a more or less extensive sequestrum. The periosteum in the early stages may be separated from the bone by a collection of pus, and in such cases it appears as a thin fibrous membrane beneath the muscles, separated from the bone by the abscess cavity. Secondary changes occur in the soft tissues surrounding the seat of an acute suppuration of bone. During the acute stage there may be a definite abscess of the soft parts, with an infiltration which simulates phlegmonous inflammation, or, by rupture of the abscess, various sinuses may be formed leading down to the necrotic foreign body. In long continued cases the skin and subcutaneous tissues become thickened by the formation of scar tissue, due to the presence of the involucrum and the persistence of sinuses, and by thickening of the soft tissues, an affected limb may for years be nearly twice its normal size. +Symptoms.+ The disease usually begins with a sharp onset, the first symptom being a sudden localized pain in the vicinity of the epiphyseal line, or in the shaft of some one of the long bones. This pain is extremely intense, and in typical cases is most excruciating.