The effects of insulin-like growth factor-I (IGF-I) on cerebellar dysfunction and neurodegeneration were investigated in leaner mice, which exhibit cerebellar ataxia and neurodegeneration related to P/Q-type calcium channel mutations. Leaner mice showed significantly reduced serum and cerebellar IGF-I concentrations compared to wild-type mice at postnatal day 30. Behavioral assessment of leaner mice injected with IGF-I subcutaneously for 4 weeks showed partially improved cerebellar function. Histological analysis of IGF-I treated leaner cerebella showed no difference in the number of dying Purkinje cells compared to control leaner cerebella. These results further support potential use of IGF-I as a therapeutic aid for cerebellar ataxia related to calcium channel mutations. Nonetheless, IGF-I administration does not rescue dying cerebellar neurons, which suggests that the beneficial effects of IGF-I may have been achieved through surviving cerebellar neurons.