In order to in vivo identify subgroups in eight patients with the clinical diagnosis of progressive supranuclear palsy (PSP), we have performed 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT), a nuclear medicine technique, to visualize dopamine D2 receptors in vivo, and high resolution (TE/TR 2900/20-90) magnetic resonance imaging (MRI) to evaluate morphological CNS changes. All patients exhibited similar clinical features including supranuclear vertical gaze palsy, especially of downward gaze, predominantly axial rigidity especially in the neck, bradykinesia, instability of balance with easy falls, and poor response to dopaminergic drugs. Specific striatal dopamine D2 receptor binding in IBZM-SPECT, as calculated by a basal ganglia to frontal cortex ratio (BG/FC) was reduced in 5 patients, but normal in 3 patients. In MRI, these 3 patients exhibited multiple hyperintense white matter lesions; 2 of them had no midbrain atrophy. In contrast, all 5 patients with reduced IBZM binding lacked multiple white matter lesions in MRI, but 4 of them showed marked midbrain atrophy. This pilot study with IBZM-SPECT for in vivo imaging of striatal dopamine D2 receptors and T2-weighted MRI supports published neuropathological findings that clinical signs of PSP appeared to be due to heterogeneous neuropathology.