BACKGROUND The exact mechanisms for antipsychotic-induced extrapyramidal side-effects have remained obscure despite intensive research. Previous studies have highlighted a central role for nigral dopamine D(2) receptors in the control of motor functions. OBJECTIVE The aim of the present study was to examine relationships between dopamine D(2) receptor binding in both substantia nigra and temporal cortex with extrapyramidal symptoms among antipsychotic-treated patients with schizophrenia. METHODS Single-photon emission-computed tomography (SPECT) ligand [(123)I]epidepride was used to determine dopamine D(2/3) apparent binding potential in 13 antipsychotic-treated (seven with clozapine, four with olanzapine and two with haloperidol) patients with schizophrenia. Extrapyramidal symptoms were assessed with the Simpson and Angus Scale (SAS). RESULTS A statistically significant correlation was observed between dopamine D(2/3) receptor apparent binding potential in the substantia nigra and extrapyramidal side-effects (r = -0.62, P = 0.024). No correlations were detected in the temporal cortex between dopamine D(2/3) receptor binding and extrapyramidal side-effects. CONCLUSIONS These findings support the role of dopamine D(2) autoreceptors in substantia nigra regarding drug-induced movement disorders.