Latent herpes simplex virus (HSV) is known to reside in the trigeminal ganglia. Our studies show that the temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals caused a striking decrease in the number of positive HSV cultures obtained during the 20 weeks immediately following surgery. We found that the stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. Stereotaxic stimulation of the trigeminal ganglion in chronically infected animals produced a significant increase in positive cultures within two days. But, direct neurosurgical stimulation of the trigeminal ganglion proved strikingly effective, producing 83% positive cultures at the eye within 48 hours of operation. These studies further substantiate the premise that the trigeminal ganglion serves as a reservoir for latent HSV from the trigeminal ganglion to its infectious form in the peripheral ocular tissues somehow involves the trigeminal nerve.