The hypothesis is that an antiviral drug (valacyclovir) will reduce the amount of Epstein-Barr virus (EBV) in the mouths of university students with infectious mononucleosis (mono) while being a safe drug. Because EBV is the cause of mono, it is expected that reduction of the amount of virus could result in faster recovery from the disease.

University of Minnesota students 18 years of age or older who are referred by the Boynton student health service during the first 7 days of infectious mononucleosis are eligible to participate. All of the subjects who enroll will be allowed to complete the study, but only the information from those students who truly have mono due to a primary infection with EBV as determined by laboratory tests will be used for the results. The students will be assigned by chance(randomized)either to receive the antiviral drug valacyclovir at a dosage of a 1 gram tablet every 8 hours for 14 days or no antiviral drug. Nine research clinic visits over 180 days are scheduled for clinical exams, histories, and collection of mouth and blood samples. The amount of EBV in the mouth and blood will be measured by a molecular virology research test called real-time TaqMan polymerase chain reaction. The severity of illness will be evaluated using a scale that measures the degree of physical activity and intensity of symptoms. The safety of the drug will be monitored by periodically checking the blood cell counts, and assessing liver and kidney function among other parameters. Personnel who do the lab work and analyze the data will not know the subjects' study drug assignments so that the data can be collected and analyzed objectively. The study will remain open to enrollment until 20 subjects with laboratory-confirmed primary EBV have been enrolled and followed for at least 2 weeks. The study will end when all subjects complete all scheduled study visits.

Inclusion Criteria:

• Clinical diagnosis of infectious mononucleosis with onset no more the 7 days before enrollment; willingness to sign informed consent
• Willingness to provide blood and oral washing samples at regular intervals
• Females must have a negative urine pregnancy test and agree to use effective contraception (barrier or hormonal) for the first 30 days of the study if assigned to valacyclovir
• Corticosteroids are permitted only if prescribed by the subject's primary physisican for treatment of this acute disease

Exclusion Criteria:

• Previous history of mono
• Pregnant or breast feeding
• End-stage renal or liver disease
• Immunosuppressed due to underlying medical disease and/or immunomodulating medications prior to enrollment
• Onset of present illness >7 days ago