Blood-brain barrier imaging of brain tumours is fast attracting interest now that it has been demonstrated that disruption of the blood-brain barrier is essential for uptake of all tumour-seeking agents. The aim of the present study was to differentiate recurrent tumour from post-radiation gliosis using (99m)technetium-glucoheptonate ((99m)Tc-GHA) as a tumour-seeking agent. Brain single photon emission computed tomography (SPECT) with (99m)Tc-GHA was performed in 73 patients with primary malignant brain tumours after radiotherapy, and the results were correlated with the clinical behaviour of the disease on follow up. The SPECT was suggestive of recurrent tumour in 55 patients. The clinical course was consistent with recurrence in 51 of the 55 patients. The clinical course was consistent with radiation necrosis in the remaining 21 patients, which included 17 patients with a negative SPECT and four patients with a positive SPECT study. Mean GHA index in recurrent tumour and post-radiation gliosis was 7.04 +/- 4.35 and 1.88 +/- 1.70, respectively (P = 0.0001). Mean GHA index in high-grade and low-grade glioma was 7.78 +/- 4.73 and 3.15 +/- 2.44, respectively (P = 0.001). (99m)Technetium-glucoheptonate brain SPECT is a sensitive and reliable diagnostic modality to differentiate recurrent tumour from post-radiation gliosis.