The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders (APD) is complicated by the presence of signs and symptoms common to both forms of parkinsonism. Metabolic brain imaging with [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be a useful adjunct in differentiating APD from IPD. To explore this possibility, we studied 48 parkinsonian patients suspected as having possible APD because of a deteriorating response to dopaminergic treatment, the development of autonomic dysfunction, or both. A group of 56 patients with likely IPD served as control subjects. We used quantitative FDG/PET to measure regional rates of cerebral glucose use in IPD and APD patients. We used discriminant analysis to categorize IPD and APD patients based on their regional metabolic data. We found that a linear combination of caudate, lentiform, and thalamic values accurately discriminated APD from IPD patients (p < 0.0001). Significant metabolic abnormalities were present in the striatum and the thalamus of 36 of 48 (75%) APD patients. Our findings show that measurements of regional glucose metabolism can be used to discriminate patients with suspected APD from their counterparts with classic IPD. FDG/PET may be a useful adjunct to the clinical examination in the differential diagnosis of parkinsonism.