The presence and specificity of axon guidance cues in the mature brain were examined by transplanting several types of xenogeneic neural cells from fetal pig brains into adult rat brains with selective neuronal loss. Committed neuronal phenotypes from cortical, mesencephalic and striatal fetal regions were implanted in homotopic or ectopic central nervous system locations. Using specific neurofilament and neural markers, axonal target selection by transplanted fetal neurons was determined throughout the central nervous system. Different types of donor neurons grew axons specifically to appropriate adjacent and distant host brain regions from ectopic or homotopic brain implantation sites and independent of the pattern of prior selective neuronal loss. Since the fetal donor neurons could orient axonal growth towards their normal synaptic termination zones, it shows that the adult brain also elaborates highly specific signals for axon guidance. These results obtained by xenotransplantation also demonstrate that the adult brain exhibits a latent potential for long-distance axon guidance that is evolutionarily conserved. These and related studies indicate that the necessary processes for connection of specific neurocircuitry also exist in the adult central nervous system, if axonal growth inhibition is overcome.