Huntington's disease (HD) is caused by the inheritance of the huntingtin gene with an expanded CAG repeat. The function of the normal or mutant form of the huntingtin protein remains to be determined. We used differential display to determine differences in steady-state mRNA levels between wild-type and the R6/2 transgenic mouse model of HD. Using this method, we determined that the steady-state mRNA levels of protein kinase C beta II (PKC beta II) subunit are decreased in symptomatic HD mice compared with age-matched wild-type controls. The decrease in PKC beta II mRNA levels occurred in both the striatum and cortex. Previously, it had been demonstrated that PKC beta II immunoreactivity is decreased in the caudate-putamen of patients with Huntington's disease. PKC has been implicated in the long-term potentiation model of brain plasticity and learning, and the loss of PKC may affect information storage in HD. The expression of htt-HD throughout the brain affects the transcription of specific genes in regions not associated with widespread neurodegeneration.