This study examined the effects of Huntington's disease (HD) on neural activity during performance of the Porteus maze task. fMRI data were acquired from three HD patients and three controls. Reduced fMRI signal was observed in the patients relative to the controls in occipital, parietal and somato-motor cortex and in the caudate, while increased signal was found in HD in the left postcentral and right middle frontal gyri. The altered fMRI responses in HD patients may result from neural, metabolic, neurovascular coupling and/or hemodynamic differences associated with this disorder.