Parkin-deficient mice exhibit nigrostriatal deficits but do not show a loss of dopaminergic neurons. The mice are viable and exhibit normal brain morphology. In vivo microdialysis reveals increased extracellular dopamine concentration in the striatum of parkin−/− mice, suggesting an increase in dopamine release from nigral neurons. Intracellular recordings of medium-sized striatal spiny neurons show reduced synaptic excitability, requiring greater currents to induce synaptic responses. Parkin−/− mice also exhibit behavioral deficits in tasks sensitive to nigrostriatal dysfunction, such as the beam traversal test and adhesive removal test. However, the number of dopaminergic neurons in the substantia nigra remains normal up to 24 months of age. Steady-state levels of parkin substrates, including CDCre1-1, synphilin-1, and α-synuclein, are unaltered in parkin−/− brains. These findings suggest that parkin plays a novel role in dopamine regulation and nigrostriatal function, while its loss does not affect the survival of nigral neurons.Parkin-deficient mice exhibit nigrostriatal deficits but do not show a loss of dopaminergic neurons. The mice are viable and exhibit normal brain morphology. In vivo microdialysis reveals increased extracellular dopamine concentration in the striatum of parkin−/− mice, suggesting an increase in dopamine release from nigral neurons. Intracellular recordings of medium-sized striatal spiny neurons show reduced synaptic excitability, requiring greater currents to induce synaptic responses. Parkin−/− mice also exhibit behavioral deficits in tasks sensitive to nigrostriatal dysfunction, such as the beam traversal test and adhesive removal test. However, the number of dopaminergic neurons in the substantia nigra remains normal up to 24 months of age. Steady-state levels of parkin substrates, including CDCre1-1, synphilin-1, and α-synuclein, are unaltered in parkin−/− brains. These findings suggest that parkin plays a novel role in dopamine regulation and nigrostriatal function, while its loss does not affect the survival of nigral neurons.