The tremendous plasticity exhibited by stem and progenitor cells raises the possibility that they can be used to replace components and restore function to parts of the brain that have been compromised by congenital disorders, developmental malfunction, injury or disease. There is, however, little understanding of the behavior and regulation of these cells in the environment of the healthy brain, or in the nervous system altered by such conditions as stroke, trauma, spinal cord injury, sensory loss, Muscular Dystrophy, Amyotrophic Lateral Sclerosis, Parkinson’s Disease, Huntington’s Disease, Alzheimer’s Disease, Multiple Sclerosis or mental illness. There are few studies on the long-term fates of transplanted cells within the nervous system or at other sites within the host. An understanding of environmental cues, age-dependent processes and genetic factors that govern the activities of these cells is crucial in order to develop safe and effective cell-replacement treatments. This Program Announcement encourages applications for support of ground-breaking research on non-human stem cells that address these issues.