The use of stem cells and other cells as therapies is still in its infancy. One major setback is the limited survival of the grafts, possibly due to immune rejection. Studies were therefore performed with human umbilical cord blood cells (HUCB) to determine the ability of these cells to survive in vivo and the effect of the immune response on their survival by transplantation into the normal striatum of immunodeficient NOD SCID mice. Long-term culture of HUCB cells resulted in several different populations of cells, including one that possessed fine processes and cell bodies that resembled neurons. Their neuronal phenotype was confirmed by immunohistochemical staining for the early neuronal marker TuJ1 and the potentially neural marker Nestin. Five days after cell transplantation of this neuronal phenotype, immunohistochemical staining for human mitochondria confirmed the presence of living HUCB cells in the mouse striatum, with cells localized at the site of injection, expressing early neural and neuronal markers (Nestin and TuJ1) as well as exhibiting neuronal morphology. However, no evidence of surviving cells was apparent 1 month postgrafting. The absence of signs of T cell-mediated rejection, such as CD4 and CD8 lymphocytes and minimal changes in microglia and astrocytes, suggest that cell loss was not due to a T cell-mediated immune response. In conclusion HUCB cells can survive long-term in vitro and undergo neuron-like differentiation. In mice, these cells do not survive a month. This may relate to the differentiated state of the cells transplanted into the unlesioned striatum, rather than T cell-mediated immunological rejection.