Treatment-refractory depressed patients who objected to electroconvulsive therapy (ECT) were given a series of anesthesias with isoflurane (Forane®), a modern and established inhalation anesthetic. According to our hypothesis to be tested, the brief period of electrocerebral silence (ES), which can be observed shortly after the grand mal seizure in ECT, may be in itself a crucial biological determinant for the therapeutic effects of ECT. Isoflurane is the only drug known to effect an ES in the EEG in nontoxic concentrations, which does not result in adverse effects on any body organ including the brain; no seizure activity can be observed. Eleven depressed patients received a total of 36 anesthesias with isoflurane (ES narcotherapy). Rapid antidepressant effects were observed in 9 patients (p < 0.0001). Effects were reproducible and lasted up to several weeks. No adverse effects of anesthesia were noticed