Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). Prospective study. Parkinson disease outpatient clinic. Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. Differences in [(123)I]beta-CIT uptake. All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.