Some complications of joint replacement surgery are easily diagnosed; however, differentiating infection from aseptic loosening is difficult because these entities are remarkably similar at clinical and histopathologic examination. Clinical signs and symptoms, laboratory tests, radiography, and joint aspiration are insensitive, nonspecific, or both. Cross-sectional imaging modalities are hampered by artifacts produced by the prosthetic devices themselves. Radionuclide imaging is not affected by the presence of metallic hardware and is therefore useful for evaluating the painful prosthesis. Bone scintigraphy is useful as a screening test, despite an accuracy of only 50%-70%, because normal results essentially exclude a prosthetic complication. The addition of gallium-67, a nonspecific inflammation-imaging agent, improves the accuracy of bone scintigraphy to 70%-80%. The accuracy of combined leukocyte-marrow imaging, 90%, is the highest among available radionuclide studies. Its success is due to the fact that leukocyte imaging is most sensitive for detection of neutrophil-mediated inflammation (ie, infection). The success of leukocyte-marrow imaging is tempered by the limitations of in vitro labeling. In vivo labeling has been investigated, and a murine monoclonal antigranulocyte antibody appears promising. Some investigations have focused on fluorodeoxyglucose imaging. Although this method is sensitive, specificity is a concern.