The huntingtin (HTT) gene, which is mutated in Huntington's disease, is expressed in non-neuronal cells as well as neurons. Here, both microglia and peripheral immune cells from newborn mutant Htt mice showed markedly impaired migration, and this impairment could be reproduced by expressing a mutant Htt fragment in microglial cell lines. Peripheral immune cells from pre-symptomatic individuals with the Huntington's disease mutation also showed impaired migration, suggesting that these immune changes contribute to the development of the disease.