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Abstract Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play important roles in the pathogenesis of HD. Since no effective treatment is available, this study was designed to explore the therapeutic potential of erythropoietin (EPO), a cytokine that has been found to prevent excitotoxicity, and to promote neurogenesis. To avoid the side effects of a raised hematocrit, we used asialoerythropoietin (asialoEPO), a neuroprotective variant of EPO that lacks erythropoietic effects in mice. R6/2 transgenic HD mice were treated with this cytokine from five to twelve weeks of age. Results We provide new evidence that cell proliferation in the dentate gyrus of the R6/2 hippocampus is reduced by 50% compared to wild-type littermate controls. However, we found that the asialoEPO treatment did not affect the progression of motor symptoms, weight loss or the neuropathological changes. Furthermore, cell proliferation was not enhanced. Conclusions We conclude that the chosen protocol of asialoEPO treatment is ineffective in the R6/2 model of HD. We suggest that reduced hippocampal cell proliferation may be an important and novel neuropathological feature in R6 HD mice that could be assessed when evaluating potential therapies.