Seventy-seven adult patients with suspected skeletal metastases were divided into two groups. In group A (n = 30), following intravenous administration of 20 mCi (740 MBq) of technetium-99m methylene diphosphonate (99mTc-MDP), 3- and 24-h scintigraphy of bone lesions was performed. The 24/3 h lesion to bone background radiouptake ratio (RUR) was calculated for each lesion. In group B (n = 47), the same procedure was followed with dexamethasone intervention (10 mg in 24 h) following the 3-h acquisition. In group A, after determination of the critical point, malignant and degenerative bone lesions could be separated with a sensitivity, specificity and accuracy of 0.76, 0.72 and 0.73, respectively. The mean RUR of the malignant lesions was 1.20 +/- 0.23, and that of the benign lesions, 0.95 +/- 0.15. In group B cases, significantly increased sensitivity, specificity and accuracy of 0.87, 0.94 and 0.92, respectively, were found (P < 0.001). The mean RUR of the malignant lesions was 1.48 +/- 0.34, and that of degenerative lesions, 0.88 +/- 0.19. Dexamethasone interventional bone scintigraphy seems to be a new cost-effective method for differentiating malignant from degenerative bone lesions using the RUR.