One of the challenges of neurological gene therapy for the treatment of chronic neurodegener-ative disorders, such as Parkinson's and Alzheimer's diseases, is achieving high levels, widespread distribution, and long-lived transgene expression in the brain. Here, following the intracerebral injection of a recombinant adenovirus (RAd) encoding herpes simplex virus type 1 thymidine kinase (HSV1-TK), we detect very high levels of HSV1-TK immunoreactivity throughout the brain both ipsilaterally and contralaterally to the injection site, for up to 12 months following vector administration. This study concludes that long-term, high-level, and anatomically distributed HSV1-TK immunoreactivity can be obtained, and that this is most likely due to transgene-specific properties, because neither the distribution nor the longevity were observed for the transgene β-galactosidase encoded by a co-injected vector. Thus, we demonstrate that transgene expression can be achieved over widespread areas of the rodent brain, even 12 months after a single injection of first-generation adenovirus vector.