Difficulties in neuronal transfection continue to restrict the applicability of molecular approaches to neurobiology. Conventional transfection techniques have been of limited effectiveness, particularly in intact neural tissues. Viral vectors effectively transfect neurons both in vitro and in vivo but are labor intensive to construct, difficult to control, and often compromise cell viability. We describe here an alternative strategy using particle-mediated gene transfer for the transfection of neurons and glia in intact brain slices. This approach is efficient, reliable, and does not require advanced molecular biological facilities for its application.