The authors present a prospective analysis of Tc-99m MDP and Tc-99m citrate scintigraphy in 29 patients who were clinically suspected of having chronic osteomyelitis. All of the patients showed increased Tc-99m MDP uptake on bone scintigraphy involving the area of concern. However, Tc-99m citrate scintigraphy clearly identified the patients with osteomyelitis (N = 18) confirmed either by biopsy or clinical follow-up. Eleven patients who were free of osteomyelitis showed only minimal radiotracer uptake on Tc-99m citrate scintigraphy. These patients had other benign musculoskeletal diseases that were diagnosed by other imaging modalities. In addition to visually interpreting the scintigraphic images, a semi-quantitative analysis was performed by drawing regions of interest over the areas involved and the normal contralateral side, and patients with osteomyelitis were found to have lesion to nonlesion ratios of greater than 1.70. Because Tc-99m MDP is a nonspecific radiopharmaceutical for the evaluation of bone infection, other imaging agents have been investigated. Tc-99m citrate is a small molecule that makes it suitable to penetrate injured capillaries to the edema fluid known to be present in areas of infection. The authors conclude that Tc-99m citrate is a promising agent for localizing and showing the extent of bone infection that will help the surgeon to determine areas of debridement before surgery.