To test the in vivo effect of a high yield of dopaminergic (DA) neurons (90% of total neurons) which had been generated from a genetically modified mouse embryonic stem cell line, N2, the cells were transplanted into a rat model of Parkinson's disease (PD). The PD animals grafted with N2-derived cells showed significant behavior improvements compared with sham controls from 2 weeks posttransplantation, whereas animals with naive D3-derived cells (similar to 28% DA neurons of total neurons) showed only a modest recovery. Furthermore, hyperactivity observed in the subthalamic nucleus, pedunculopontine nucleus, and substantia, nigra pars reticulata of PD rat models was dramatically reduced by the grafting of N2-derived cells. The number of DA neurons in the striatum which originated from N2 grafting was much higher compared to that from D3 grafting, and the neurons efficiently released DA in the brain, showing a good correlation with behavioral recovery. (c) 2005 Elsevier Inc. All rights reserved.