The purpose of this study was to compare striatal D2 dopamine receptor occupancy of various typical neuroleptics and clozapine in relation to the occurrence of extrapyramidal side effects (EPS). Forty-four inpatients with schizophrenia, including 12 patients with schizodominant schizoaffective disorder, were evaluated using 123I-iodobenzamide (IBZM) and single photon emission computed tomography. Striatal D2 dopamine receptor occupancy was estimated by use of a striatal/frontal cortex ratio (ST/FC) of IBZM binding. Fourteen patients were neuroleptic-free and served as controls. Six patients were treated with clozapine and 24 patients were treated with various typical neuroleptics. ST/FC ratios in patients taking typical neuroleptics were significantly lower than those who were neuroleptic free or treated with clozapine. Patients with EPS had lower ST/FC ratios than those without EPS. A significant linear relationship between ST/FC ratios and severity of EPS estimated by the Simpson-Angus-Scale was established (r=-0.51, p=0.041).