A group of 63 patients with disease of the brain was investigated with methetharimide ([beta],[beta]-methylethylglutarimide), an activating and convulsant agent. Particular attention was paid to focal eeg changes and focal aspects of induced seizures. Clinical effects of the drug were mild. No mortality and no significant morbidity occurred. General eeg''activation of slowing and spikes was commonly produced. Response to visual (photic) stimulation was markedly increased by the drug, and flicker often produced myoclonus. Early focal eeg changes on the side of the lesion were produced in 12 of 28 patients with unilateral brain disease and in 7 of 14 patients with both unilateral and diffuse brain disease. In contrast, 18 of 19 patients with diffuse brain disease had only diffuse eeg changes. Grand mal seizures were induced 33 times in 26 patients; 2 patients had psychomotor seizures, and 1 had a focal visual sensory seizure. In the grand mal seizures, head and eye turning was commonly seen but could not be correlated with unilateral brain disease. On the other hand, tonic one-sided body movements, mostly of the arms, occurred in 13 of 20 patients with unilateral brain disease. In 11 of these 13, they were contralateral to the diseased side and were ipsilateral in 2. Focal clonus appeared only in patients with unilateral brain disease and was contralateral in 6 of 7. Myoclonus had no lateralizing value. Postictal weakness was a reliable sign but did not occur frequently. Patients who had eeg foci or focal clonus were generally not those who had focal signs during induced grand mal seizures. Methetharimide appears to be safe for eeg activation and has been valuable for the study of induced seizures in patients with brain disease. Although, errors in lateralization have been noted, activation appears to be a useful supplement in diagnosing unilateral brain disease.