This chapter discusses certain critical questions, such as whether dopamine neurons are responsible for reversal of parkinsonism, or whether some other element of the neuropil, such as glia or released trophic factors may be essential, by the inclusion of control transplants of cerebellar tissue derived from the same fetal brains that were used for substantia nigra grafting. The chapter also proposes a new approach that allows a precise comparison of dopamine levels, measures neurochemically, and the presence of dopamine neurons in and near graft sites. The presence of dopaminergic neurons with fibers that extended from the graft into the host, especially within the boundaries of the punched regions, strongly supports the concept that dopamine is in a position anatomically to integrate with host brain activity. Fetal nerve cell grafts, probably, are lasting therapeutic interventions in experimentally induced Parkinsonism in a primate species closely related to human. The lack of any rejection and the development of an extensive anatomical substrate for integration with the host brain indicate that the procedure of grafting neurons possesses exciting possibilities for therapeutic intervention in human parkinsonism. Dopamine neurons are an essential component of the graft for promoting functional recovery in severely debilitated, l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridin (MPTP) treated animals. However, more information is needed regarding the developmental, immunological and transmitter phenotype characteristics of immature human neurons that might aid or optimize their transplantation. © 1988 Academic Press Inc.