The cause of hand and wrist pain can be difficult to determine, especially when standard radiographs are normal or show only nonspecific changes. This study reports the effectiveness of radionuclide imaging in the evaluation of patients with hand and wrist pain of uncertain cause. Eighty-eight patients with hand and wrist pain and initially normal standard radiographs were evaluated prospectively by additional radiographic methods including the following: routine tomography, wrist arthrography, computerized tomography, or magnetic resonance imaging. Each patient also had bone scintigraphy. The diagnosis established by clinical assessment and by other imaging methods was then compared with the scintigraphic findings. The presence or absence of focal scintigraphic abnormalities correlated with the presence or absence of focal pathology definable by the conventional methods in 88% of patients. As expected, scintigraphy was chiefly of value in defining the locus of an injury or other process in the wrist, rather than the nature of an abnormality. The scintigrams were abnormal in 95% of cases involving complete intrinsic ligament ruptures and fractures and were normal in 96% of patients with no definable injury. Scintigraphic findings correlated poorly with partial intrinsic ligament injuries and in cases of synovitis. Radionuclide imaging is a sensitive means of detecting focal lesions in patients with hand and wrist pain of unknown cause.