Gene transfer to the central nervous system (CNS) is complicated by the anatomic and physiologic isolation of the brain. Direct injection techniques circumvent this, and allow delivery of transgenes to specific areas of the CNS. Previously, direct transfection of cellular components of the CNS has been achieved using plasmid DNA. We report the use of cationic liposomes as a means of transfecting plasmids into adult mammalian brain. Using the gene for E. coli beta-galactosidase or the cDNA or human beta-glucuronidase as reporters, we demonstrate plasmid mediated gene transfer into the caudate putamen of adult mice with expression of the transgene for at least 21 days post-transfection.