Inclusion Criteria:

• Must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received AdV-tk + prodrug on this study may receive an additional AdV-tk + prodrug course at recurrence if eligibility criteria are still met.
• Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
• Must be planning to undergo standard radiation therapy.
• Performance status KPS 70 or more.
• SGOT (AST) < 3x upper limit of normal.
• Serum creatinine < 2mg/dl and calculated creatinine clearance >10ml/min.
• Platelets > 100,000/mm3 and WBC > 3000/mm3.
• Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
• Must give study specific informed consent prior to enrollment. For re-administration, patients must be re-consented.
• Must be able to tolerate MRI scan procedure

Exclusion Criteria:

• Active liver disease including cirrhosis or hepatitis
• Patients on immunosuppressive drugs (with exception of corticosteroid)
• Known HIV+ patients.
• Acute infections (viral, bacterial or fungal infections requiring therapy).
• Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
• Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
• Other serious co-morbid illness or compromised organ function.
• May not receive chemotherapy until valacyclovir completed
• May not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from AdV-tk injection until tumor progression).