Herpes simplex virus type 1 (HSV-1) reactivates from the nervous system and causes recurrent disease in end organs such as the eye and the lips. We found that the P-adrenergic receptor blocker, propranolol, reduces HSV-1 reactivation in an animal model. Mice latent for McKrae strain HSV-1 were injected with propranolol or saline once a day for 3 successive days, and subjected to a brief period of hyperthermia on the second day to induce reactivation. Twenty-four hours after the third injection, swabs of the ocular surface and homogenates of the corneas and trigeminal ganglia were analyzed for the presence of infectious virus and viral DNA. Treatment with propranolol significantly decreased the appearance of infectious virus in the tear film, cornea, and trigeminal ganglia (P < 0.05, chi(2)-test). The results suggest a possible new pharmacologic approach to suppressing herpesvirus reactivation in the nervous system and thereby preventing recurrent disease.