Thallium-201 chloride (201T1) has been used to determine regional perfusion in the myocardium and in tumors. This study was done to determine the potential prognostic importance of lesion tracer uptake to regression, local control, and rate of distant metastasis in 14 patients with neoplasms of soft tissue. Most patients had planned resections following preoperative radiation therapy. Minimum follow-up was 4 years. The ratio of nuclide uptake in the tumor to surrounding normal tissue was used as an estimate of relative blood flow. Tumors with acute volume responses (greater than or equal to 50% at the completion of X irradiation) had lower 201T1 uptake indicating lower relative blood flow than tumors that failed to have a volume reduction [1.63 +/- 0.30 (n = 9) vs 3.49 +/- 0.41 (n = 5) 201T1]. All patients had local tumor control. Patients with high uptake tumors tended to develop metastases at a higher frequency, although this was not statistically significant (p = 0.10). We conclude that 201T1 scans are a safe, non-invasive method of estimating tumor perfusion which can be useful to predict acute response to radiation, and may help to identify patients who will ultimately develop distant metastases.