The authors present a prospective analysis of Tc-99m MDP and Tc-99m citrate scintigraphy in 108 patients with known malignant or degenerative benign bone disease. Of 108 patients, 59 (group A) had malignant bone disease. The other 49 patients (group B) had degenerative benign bone disease for which the results of Tc-99m MDP scans were positive. In both groups the Tc-99m citrate scan was performed 1 week after the Tc-99m MDP scan. The Tc-99m citrate/Tc-99m MDP lesion-to-background radioisotope uptake ratio (RUR) was calculated for each lesion 3 hours after radionuclide administration. The mean RUR for the malignant lesions was 1.0 +/- 0.484; for the benign lesions, the RUR was 0.29 +/- 0.250. Static imaging was also done for 10 lesions each from the malignant and benign groups at 1, 3, and 24 hours to study the kinetics of Tc-99m citrate. Time-activity curves for malignant lesions showed that the RUR remained high for 24 hours, whereas benign lesions showed a drastic decrease at 3 and 24 hours compared with the 1-hour images. The ratio of Tc-99m citrate to Tc-99m MDP is a promising parameter to differentiate malignant from benign degenerative lesions seen as areas of increased activity on Tc-99m MDP bone scans. The sensitivity and specificity of this technique were 97.8% and 95%, respectively.