In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor, REST. Emerging evidence suggests that, in addition to protein-coding genes, non-coding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, non-coding targets of REST. This identified Human Accelerated Region 1 (HAR1), a rapidly-evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared to unaffected individuals. These data represent further evidence that non-coding gene expression changes accompany neurodegeneration in Huntington's disease. Key words: Huntington's Disease, HAR1, noncoding RNA.