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Indications for high dosage neuroleptics have become increasingly more debatable with recent emphasis on outpatient community management of the severely ill schizophrenic patient. Early studies suggest that high dose neuroleptics have greater effectiveness with some schizophrenic patients while remaining low in toxicity. As part of a rater blind study, 16 patients with the diagnosis of either chronic undifferentiated or chronic paranoid schizophrenia were placed on standard dose piperacetazine following a washout period. The dosage was then gradually increased until the patient achieved maximal effect with a minimum of side effects. Eight patients required standard dose (25-160 mg/day) while the remaining eight required high dose (160-400 mg/day). The two clinical groups are compared for therapeutic efficacy and toxicity. High dose piperacetazine was found to be effective in seven patients refractory to low dosage. Although the incidence of side effects was higher with the high dose patients, toxicity (liver, blood, renal) was not increased in patients requiring high dose medication. Indications for high dose neuroleptics are briefly discussed.