Previous research shows that transplanted stem cells have the capacity to fuse with the cells of the host, including cells within the central nervous system. In particular, bone marrow derived stem cells (BMDCs) are fusionogenic with Purkinje cells in the cerebellum. Complete cell fusion results in a binucleated cell and requires the membranes of the two cells to share their cytoplasmic constituents. To date, fusion in the brain has not been reported after transplantation of embryonic stem cells (ESCs). However, our laboratory transplants ESCs into targeted areas of the brain in rat models of focal neurological disease, and we have data indicating possible cell fusion both at the target site and elsewhere in the brain. We use a combination of techniques including immunohistochemistry, immunofluorescence, confocal microscopy and electron microscopy to show evidence of an early event of potential cell fusion, which we have termed the ?Snuggle Phenomenon?; our transplanted stem cells migrate away from the transplanted area and can be detected in close proximity to, or within, endogenous cells. The contact enables the membranes to interact, leading to expression of stem cell gene (including potentially therapeutic transgenes) expression in the host neuron. These data have important implications in the interpretation of transplantation studies and the eventual use of stem cells for the treatment of diseases of the central nervous system.