longterm survival in a rodent model of disseminated brain tumors by combined intrathecal delivery of herpes vectors and ganciclovir treatment brain tumors that have disseminated into cerebrospinal fluid csf pathways are an unresolved therapeutic problem especially in pediatric neurooncology here a gene therapy approach using the herpes simplex virus type 1 thymidine kinase hsvtkganciclovir gcv paradigm was tested using an hsv vector in a rodent model of disseminated central nervous system tumors 9lgliosarcoma cells were implanted simultaneously into the brain and the csf of syngeneic rats five days later resulting intracerebral and leptomeningeal tumors were treated by intrathecal injection of a replicationconditional hsv vector this vector was defective for the ribonucleotide reductase gene but contained an intact hsvtk gene systemic gcv treatment was started 2 days after vector application and continued for 14 days tumorfree longterm survival lts was achieved in 90 of the animals treated with this combined therapeutic approach whereas only 30 lts was found in animals that had received the vector alone and 10 lts in untreated animals this therapeutic response probably involves oncolytic onsite replication of the vector activation of gcv by a hsvtk and a strong immune response both to the vector and to 9l cells apparent vectorrelated mortality was observed in 20 of animals without subsequent gcv therapy but no vectorrelated mortality was found when the animals were treated with gcv after vector application given the successful outcome of this experimental treatment and the apparent potential of gcv to control hsvrelated toxicity intrathecal application of hsv vectors combined with gcv treatment may be a promising approach for treatment of disseminated brain tumors