Forty-eight episodes of osteomyelitis, 30 acute and 18 chronic, were evaluated in a prospective multicenter collaborative study to determine whether a standardized serum bactericidal test could predict outcome of infection. All centers used a microdilution test method that defined the recognized important test variables, including inoculum size, culture medium, dilution technique, incubation time, method of subculture, and bactericidal endpoint. In patients with acute osteomyelitis, peak serum bactericidal titers had no predictive value; however, trough titers of 1:2 or greater accurately predicted cure, whereas trough titers of less than 1:2 predicted therapeutic failure. In patients with chronic osteomyelitis, peak serum bactericidal titers of 1:16 or greater and trough titers of 1:4 or greater accurately predicted cure, whereas peak titers of less than 1:16 and trough titers of less than 1:2 accurately predicted failure. It is concluded that this standardized serum bactericidal test provides good prognostic information in patients with osteomyelitis, and it is recommended that patients with acute osteomyelitis have serum bactericidal titers of 1:2 or greater at all times and that patients with chronic osteomyelitis have serum bactericidal titers of 1:4 or greater at all times.