Antipsychotic-induced D2 receptor occupancy values tend to be lower when measured with [ 123 I]IBZM SPECT than with [ 11 C]Raclopride PET. To clarify this issue, D2 receptor occupancy was measured in the same subjects using both techniques. Twenty patients with schizophrenia on monotherapy with risperidone (n=7; 3–9 mg/d), olanzapine (n=5; 5–20 mg/d) or clozapine (n=8; 150–450 mg/d) at stable doses, and ten healthy volunteers (HV) underwent both a [ 123 I]IBZM SPECT and a [ 11 C]Raclopride PET examinations in random order on different days within a week. Patients with schizophrenia were scanned at a fixed interval after last dose administration. Quantification of receptor availability was performed using the most conventional methods from the literature: the tissue ratio derived specific uptake ratios (SUR) were used for SPECT, and simplified reference tissue model (SRTM) derived binding potentials (BP ND ) for PET. Analysis was performed using both occipital cortex and cerebellum as reference regions for both modalities. Striatal D2 receptor occupancy was measured as the percentage reduction of [ 123 I]IBZM SUR or [ 11 C]Raclopride BP ND compared to the population average measured in HV using the same modality. Occupancy values measured by SPECT were lower than those measured with PET, by 12.4% and 13.8% when occipital cortex and cerebellum were used as reference regions. This difference should be taken in consideration when interpreting reported antipsychotic striatal D2 receptor occupancy values from the literature.