Thirteen treatment-resistant, chronically institutionalized schizophrenic patients on high-dose neuroleptic (the equivalent of at least 50 mg of haloperidol (HPL) daily) were transferred to a special research ward for a trial of systematic dosage reduction. In these 13 patients, it was possible to reduce the dose of HPL from 63.1 mg/day (SD +/- 12.5, range = 50-80 mg/day) to 23.1 mg/day (SD +/- 16.3, range = 0-65 mg/day) over a mean period of 32 weeks (SD +/- 9.6, range = 15-46 weeks). Their total Brief Psychiatric Rating Scale (BPRS) scores were improved (p = .04), they definitely experienced fewer extrapyramidal side effects (p = .01), and 6 of the patients showed global improvement. On several behavioral rating scales there was, if anything, an improvement in negativistic behavior. The substantial dosage reduction was paralleled by a comparable drop in plasma levels. HPL plasma levels at baseline were 38.8 ng/mL (SD +/- 17.8, range = 21.5-69.5 ng/mL) and at the lowest effective dose were 12.4 ng/mL (SD +/- 10.3, range = 0-43.4 ng/mL).