The purpose of this review is to summarize emerging evidence that the neurobehavioral features of Lesch-Nyhan disease (LND), a developmental disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), may be attributable to dysfunction of the basal ganglia. Affected individuals have severe motor disability described by prominent extrapyramidal features that are characteristic of dysfunction of the motor circuits of the basal ganglia. They also display disturbances of ocular motility, cognition, and behavioral control that may reflect disruption of other circuits of the basal ganglia. Though neuropathologic studies of autopsy specimens have revealed no obvious neuroanatomical abnormalities in LND, neurochemical studies have demonstrated 60-90% reductions in the dopamine content of the basal ganglia. In addition, recent PET studies have documented significant reductions in dopamine transporters and [18F]fluorodopa uptake in the basal ganglia. These findings support the proposal that many of the neurobehavioral features of LND might be related to dysfunction of the basal ganglia.