The aim of the present study was to identify brain electrical activity changes generated by olanzapine (OLZ) in treatment refractory schizophrenics (TRS). 14 paranoid TRS (31.5+/-8.39 years old) were evaluated before and after 8 weeks of OLZ treatment. Psychopathology was evaluated by means of total BPRS and PANSS scores. Resting EEG was recorded in the pre (under typical neuroleptics) and post (under OLZ) sessions. A good response to OLZ was observed in 57% of TRS. A significant reduction in positive and negative symptoms scales of PANSS was found. Absolute power of theta1, theta2, alpha1 bands increased after treatment, while beta2 power showed a decrease. Intrahemispheric correlation increased between different zones of the frontal areas and between frontal and posterior areas, while interhemispheric correlation decreased in theta2. EEG changes were more evident in those patients who had a better response to OLZ. OLZ showed to be effective in TRS, improving psychiatric symptoms and increasing activity synchronization between different areas within each hemisphere that may indicate a functional reorganization, particularly in good responders.