Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH function in noradrenergic cells. These DA-deficient (DA−/−) mice were born at expected frequency but became hypoactive and stopped feeding a few weeks after birth. Midbrain dopaminergic neurons, their projections, and most characteristics of their target neurons in the striatum appeared normal. Within a few minutes of being injected with l-dihydroxyphenyla-lanine (l-DOPA), the product of TH, the DA-−/− mice became more active and consumed more food than control mice. With continued administration of l-DOPA, nearly normal growth was achieved. These studies indicate that DA is essential for movement and feeding, but is not required for the development of neural circuits that control these behaviors.