We investigate the application of gene therapy for the treatment of malignancies of the CNS. Several different projects constitute that goal and include: a clinical trial using in vivo, retroviral-mediated, transfer of the herpes simplex thymidine kinase gene (HStk) into malignant brain tumors followed by intravenous ganciclovir, preclinical study of HStk-gene transfer for the treatment of meningeal carcinomatosis, preclinical studies of other viral vectors for gene therapy, and studies of the distribution mechanics of viral-sized particles in normal brain and tumors.