The aim of this retrospective study was to assess the contribution of thallium-201 single-photon emission tomography (SPET) in the detection and differential diagnosis of brain tumours. In 90 patients 201Tl SPET was performed because of clinical or radiological suspicion of tumoral invasion, completed by technetium-99m hexamethylpropylene amine oxime and 99mTc-sestamibi SPET in some patients. For all tumours, diagnosis was based on biopsy or autopsy. Other diagnoses were made only after clinical and radiological follow-up for at least 6 months. Histologically tumours consisted of astrocytoma stage I or II (number of patients, n = 6), astrocytoma stage III (n = 8), glioblastoma multiforme (n = 14) and oligodendroglioma (n = 3), brain metastasis (n = 14), lymphoma (n = 3), meningioma (n = 3), pituitary adenoma (n = 2), pineal tumour (n = 1), colloid cyst (n = 1) and craniopharyngioma (n = 1). False-negative studies included pineal tumour (n = 1), colloid cyst (n = 1), craniopharyngioma (n = 1), astrocytomas stage I or II (n = 6) and stage III (n = 3), oligodendroglioma (n = 2) and metastasis in the brain stem (n = 1). Additional metastases approximately < 1.5 cm were not detected in two patients and 201Tl SPET underestimated tumoral extent in one patient suffering from glioblastoma multiforme (n = 1). A false-positive study was obtained in a patient with skull metastasis (n = 1). All 15 patients who were finally shown to suffer from ischaemic infarction had a normal SPET study 9-28 days after the onset of symptomatology. Of five patients with haemorrhagic infarction, studied within 2 weeks, four were false-positive. Of six patients with intracranial haemorrhage, studied 9-39 days later, one showed focal 201Tl accumulation. Two further false-positive studies consisted of angioma and epidural haematoma. Finally, SPET studies were normal in six patients with definite diagnosis of (reactive) gliosis (n = 3), Binswanger's encephalopathy (n = 1), postinfectious encephalopathy (n = 1) and multiple sclerosis (n = 1). In the patient population presented, sensitivity of 201Tl SPET for supratentorial brain tumours was 71.7% and specificity was 80.9%. Clinical information and control SPET studies in combination with early, 30-min and 3- to 4-h delayed imaging may be expected to improve on these figures. On the other hand it seems that, in addition to tumoral histology, the presence of tumours in the fossa posterior and small volumes contribute to the occurrence of false-negative 201Tl SPET studies.