Twenty-eight pressure sores were evaluated prospectively. Osteomyelitis was reported histologically in nine of 28 bones and pressure-related changes were reported in 14 bones. Roentgenograms suggested the presence of osteomyelitis in four instances of histologically proved osteomyelitis. Technetium Tc 99m medronate bone scans were highly sensitive, showing increased uptake in all cases of osteomyelitis; however, increased uptake also occurred commonly in uninfected bones due to pressure-related changes or other noninfectious causes. Cultures of bone biopsy samples usually disclosed anaerobic bacteria, gram-negative bacilli, or both. The diagnosis of osteomyelitis must be considered if a pressure sore does not respond to local therapy. If the technetium Tc 99m medronate uptake is increased in the involved area, or roentgenographic findings are abnormal, the diagnosis can only be made with certainty by histologic examination of bone. Antibacterial treatment should be selected based on the results of bone culture.