This chapter discusses the effect of insulin-like growth factor-II (IGF-II) on fetal medial septal-diagonal band cholinergic cells transplanted into the adult rat hippocampal formation (HF). IGF-II has a beneficial effect on cholinergic tissue transplanted into the mammalian central nervous system (CNS). Transplant potentiation has been determined by the evaluation of a variety of cellular responses, including neurite outgrowth, cell survivability, and neurochemical and behavioral function. NGF has been demonstrated to promote sympathetic graft fiber outgrowth, enhance cholinergic graft choline acetyltransferas (ChAT) activity, and maintain adrenal medullary graft survival and function, indicating that a growth factor may have different effects on different cell populations and transplantation models. Other less well-defined growth factors, such as injury-induced neuronotrophic factors and an NGF-like factor have also been reported to potentiate neuronal transplantation into the CNS, indicating that at least several potentiating factors have yet to be identified. As the presence of insulin-like growth factor II (IGF-11) and its receptor in the CNS and in light of its reported neurotrophc effects on neuroblastoma cells and peripheral neurons, IGF-II may have trophic effects on neurons transplanted into the CNS.