The effects of early brain damage are often, but not always, milder than the effects of comparable damage in adults, depending on the age at which injury occurred, the region of the brain damaged, and the brain functions involved. Studies of the impact of early brain damage have generally focused on functions primarily associated with the neural structures injured, even though the development and function of distant but interconnected neural systems might also show effects. Here we examine the regulation of striatal dopamine by the dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or adult lesions of the medial-temporal lobe and in normal animals. We use microdialysis to measure the dopamine response in the caudate nucleus after the infusion of amphetamine into the dorsolateral prefrontal cortex. Normal animals and those with adult lesions showed a reduction in dopamine overflow; in contrast, monkeys with neonatal lesions showed increased dopamine release. Thus, early injury to the primate medial-temporal lobe disrupts the normal regulation of striatal dopamine activity by the dorsolateral prefrontal cortex during adulthood. Early focal lesions may have substantial and long-lasting impacts on the function of a distant neural system.