We compared perfusion of prefrontal, motor, and sensory cortices and basal ganglia in 29 Huntington's disease (HD) patients and nine controls. We found a significant reduction in perfusion in patients with HD of short (< 6 years, n = 10), medium(6 - 10 years, n = 8), and long duration (> 10 years, n = 11) compared with controls. Among short-duration patients, we observed decreases in cortical perfusion before evidence of atrophy on magnetic resonance imaging, suggesting that decreases in neuronal activity, as reflected by perfusion levels, precede gross structural changes. As expected, decreased perfusion was marked in basal ganglia. The extent of cortical perfusion correlated with clinical assessments of functional capabilities as well as with the duration of disease. Prefrontal perfusion correlated with cognitive measures, and motor cortical pwefusion correlated with physical disability and activities of daily living scores. We found no significant clinical correlations with sensory cortical perfusion. Singlg-photon-emission computed tomography may be a sensitive method for assessing disease progression in clinical trials and pharmacologic intervention.