In the current experiments, we address the emerging hypothesis that transplanted neural precursor cells can respond to local microenvironmental signals in the post-developmental brain and exhibit patterns of differentiation that depend critically on specific location within the brain. HiB5 precursor cells were transplanted into adult mouse cortex, corpus callosum, and multiple positions in striatum, and assessed for differentiation by morphology and immunocytochemistry. Our results indicate that the likelihood of both neuronal and glial differentiation of transplanted precursors depends on proximity to the medial striatum or subventricular zone of the adult host, supporting the concept that microenvironmental signals can critically affect the differentiation fate of neural precursors, and suggesting the potential to manipulate such signals in the adult brain.