Changes in brain images with single photon emission computed tomography (SPECT) using technetium-99m hexamethyl-propyleneamine oxime (99mTc HMPAO) before and after intramuscular injection of haloperidol (0.08 mg/kg) were studied in 2 unmedicated schizophrenic patients and 2 normal controls by a new technique, i.e. subtraction of brain images. The haloperidol injection reduced regional cerebral blood flow extensively in the bilateral cerebral hemispheres in one of the schizophrenics and one of the normal controls, with little or no haloperidol-induced effects in the remaining 2 subjects. The widespread cortical reduction is considered to be due to a nonspecific or indirect effect of haloperidol in view of the broad action sites inconsistent with the known anatomy of the mesocortical dopaminergic system.