This study attempts to characterize thallium-201 (201TI) uptake in patients with bone and soft-tissue sarcoma and to compare these findings with gallium-67 (67Ga) and bone scintigraphy with emphasis on evaluating tumor viability before and after chemotherapy. Thirty-eight patients with surgically-proven sarcomas were evaluated. All patients had gallium and thallium studies. Nineteen patients underwent pre- and post-chemotherapy thallium and evaluation. Seven patients also had technetium-99m-MDP (99mTc-MDP) bone scintigraphy comparisons. Pathologic changes pre- and postchemotherapy were graded on the basis of %tumor necrosis as defined histologically. Scintigraphic comparisons demonstrated a high degree of correlation with 201TI and poor correlation with 99mTc-MDP. Thallium-201 was superior to 99mTc-MDP and 67Ga in predicting tumor response to chemotherapy as determined by %tumor necrosis determined histologically. Gallium was superior to Tc-MDP in predicting response to chemotherapy. However, both 67Ga and 99mTc-MDP appear to be affected by factors other than tumor activity.