Electroencephalographic (EEG) coherence is an index of brain regional coupling that has been found to be abnormal in people with schizophrenia but has not been systematically examined in response to neuroleptics. EEG coherence in slow (delta and theta) frequencies was assessed in 17 treatment-resistant people with schizophrenia at baseline, 2 hr after their first oral dose (25 mg) and after 6 weeks of clozapine treatment. Compared with EEG norms, participants exhibited significant interhemispheric and intrahemispheric coherence abnormalities prior to treatment. Both acute and chronic treatments altered coherence but differed with respect to their relationship to symptom reduction and their ability to normalize or augment pretreatment abnormalities. Findings are discussed in relation to "disconnection" theories of schizophrenia.