We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilson's disease (WD). The rCMRGlc was determined in the basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly (r = -0.80) with the reduction of striatal rCMRGlc. Clinical scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients.