To assess whether thallium-201 thallous chloride (Tl) can detect childhood tumors and whether diagnostic effectiveness improves with combined blood flow imaging, 28 children (1.0-18.6 years) were studied using single photon emission computed tomography (SPECT): Tl (1.3-1.8 mCi intravenously), followed in 13 of the patients by technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO; 8-18 mCi intravenously). Tl-uptake was markedly increased with histologically confirmed recurrent brain tumors (N = 12). Tl-avid tumors comprised several histologic types, including 6 astrocytomas/gliomas as well as nonastrocytic neoplasms, such as medulloblastoma and ependymoma. A questionable false-positive study was observed with a treated medulloblastoma. Tl failed to detect 5 tumors (i.e., 2 medulloblastomas, 1 ependymoma, 1 malignant schwannoma, and initially 1 low-grade astrocytoma). The sensitivity and specificity of 201Tl-SPECT for detection of childhood brain tumors was 76.9% and 93.3%, respectively. The mean tumor-to-normal brain ratio for Tl was 2.5 +/- 0.5 (N = 7). In some of the patients, 201Tl-SPECT allowed a more precise assessment of the functional state of the tumor than was possible with computed tomography and magnetic resonance imaging. HMPAO distribution was variously normal, increased or decreased at the site of tissue abnormality, and abnormal blood flow was demonstrated in the remaining neuraxis, in 3 of the 7 patients. Changes in tissue perfusion did not correlate with Tl findings, but were evaluated in only one false-negative study.