The potential role of thallium-201 (201Tl) scintigraphy in the imaging of various musculoskeletal tumors was investigated in 80 patients. Uptake of 201Tl was observed in 17 (100%) malignant bone tumors, 6 (100%) giant cell tumors, and 2 of 8 (25%) benign bone tumors. Nineteen of 30 malignant soft tissue tumors (63%) were positive for 201Tl scintigraphy, while 2 of 14 benign soft tissue tumors (14%) yielded positive results. None of 6 liposarcomas were visualized by 201Tl scintigraphy. There was no 201Tl uptake in the tissues of 5 non-tumorous conditions. Ten patients with osteosarcoma were evaluated by 201Tl scintigraphy both pre- and post-chemotherapy. There was a significant correlation between changes in tumor-to-normal count ratio and percent necrosis of the resected tumor. The mean decrease in tumor-to-normal count ratio was 71% for patients with >/=90% tumor necrosis and 26% for those with <90% tumor necrosis. Serial 201Tl scintigraphy, with quantitative analysis of alterations in 201Tl uptake, may provide a quantitative and objective measure of the effect of preoperative chemotherapy in patients with malignant bone tumors.