This is the first report on a controlled study comparing the therapeutic and non-therapeutic (side) effects of electroconvulsive treatment (ECT) and isoflurane narcotherapy (ISONAR; deep anesthesias with the inhalation of anesthetic isoflurane) in drug-refractory, severely depressed women, who had been randomly allocated either to ECT (n = 10) or ISONAR (n = 10). Patients from each group were subjected to a total of six treatment sessions (two sessions per week) and maintained on a fixed antidepressant drug dose. The antidepressant efficacy of either treatment was evaluated for each treatment session (in search of a 'rapid antidepressant effect') and at weekly intervals. Cognitive functions or signs of an organic brain syndrome were evaluated by means of psychological tests and extensive EEG analyses. Rapid antidepressant effects of the first treatment session were only significant in patients on ISONAR; in the subsequent treatment sessions, ECT also induced rapid antidepressant effects. Antidepressant effects during the treatment period were comparable, and patients on ISONAR improved further during follow-up, whereas patients on ECT tended to relapse. ISONAR-treated patients improved in most psychometric variables, whereas patients on ECT deteriorated. Finally, the EEG patterns of the ISONAR-treated patients remained normal or augmented (dominant alpha power), whereas patients on ECT developed an increase in abnormalities in EEG patterns and theta/delta power. This indicates an organic brain syndrome in patients on ECT.