Inclusion Criteria:

• Must have presumed malignant glioma based on clinical and radiologic evaluation and pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined
• 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.
• Must be able to tolerate MRI scan procedure

Exclusion Criteria:

• Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection.
• 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).
• Prior radiation therapy to the brain or prior treatment for brain tumor (except prior biopsy or subtotal resection).
• Other serious co-morbid illness or compromised organ function.
• May not receive temozolomide 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 study entry until tumor progression).