Huntington's disease (HD) is a progressive neurodegenerative disorder for which there is no treatment. Prior to the onset of symptoms, abnormal protein aggregates (inclusions) are found in neurons in humans and R6/2 mice. It has been suggested that the progression of HD can be slowed or prevented by disruption of the aggregation process. In agreement with this, it has been reported that systemic treatment of R6/2 mice with Congo red caused a reduction in numbers of striatal inclusions and an improvement in motor symptoms and survival [Sanchez, I., Mahlke, C., Yuan, J., 2003. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature 421, 373-379]. Here we attempted to replicate this study. We extended the experiment to include measurement of the effects of Congo red on cognitive function in R6/2 mice. Congo red treatment failed to ameliorate either motor or cognitive deficits in R6/2 mice. We suggest that this is due to the inability of Congo red to cross the blood-brain barrier. Since it does not improve the behavioural deterioration that is a key feature of HD, Congo red is unlikely to be useful as a therapy for HD.