The potential clinical efficacy of tiagabine for control of status epilepticus was evaluated in an experimental model. Tiagabine was administered to cobalt-lesioned rats in which status epilepticus was induced by injection of homocysteine thiolactone. Tiagabine was effective in controlling status epilepticus in this model; the median effective dose for control of generalized tonic-clonic seizures in the model was 8.3 mg/kg. Tiagabine administration produced an abnormal, hypo-reactive behavioral state which was accompanied by an EEG pattern of high-amplitude, frontally dominant, rhythmic, 3-5-Hz spike-wave activity. This EEG and behavioral syndrome could be reproduced by administration of tiagabine to normal, non-epileptic rats. The exact nature of this syndrome remains unclear, but whether it is an epileptic or encephalopathic phenomenon, further study is clearly required before this drug should be considered for use in the treatment of human status epilepticus.