Absence seizures and their electroencephalographic correlate, 3Hz generalised spike-wave activity, are the hallmark of idiopathic generalised epilepsy. The anatomical and neurochemical basis of absence seizures is, however, uncertain. Most research in this area has been performed in animal models. Positron emission tomography (PET) is a technique which allows non-invasive study of local tissue physiology in vivo in humans. PET was used to study cerebral blood flow during absence seizures and to examine the role of benzodiazepine-GABA_A and opiate receptors both inter-ictally and during absence seizures in patients with idiopathic generalised epilepsy. Selective focal increases in blood flow were seen in thalamus providing evidence for involvement of this structure in the pathogenesis of absence seizures. This finding supports the limited neurophysiological data in humans and is in agreement with depth EEG recordings in animal models of absence seizures. Benzodiazepine-GABA_A receptor binding was normal inter-ictally and remained unchanged during absence seizures suggesting that benzodiazepine-GABA_A receptors do not have a major role in the pathophysiology of absence seizures. Treatment with valproic acid, however, was associated with a global reduction in benzodiazepine-GABA_A receptor density. The mechanism of action of valproic acid is uncertain and this observation may be relevant to its suppression of seizures in idiopathic generalised epilepsy. No abnormality of opiate receptors was found inter-ictally but evidence was obtained for the release of endogenous opioids in neocortex at the time of absence seizures. The latter suggests that opioid transmission may have a role in the pathophysiology of absence seizures in man.