Latent herpes simplex virus (HSV) has been demonstrated in the trigeminal ganglia of experimentally infected rabbits between episodes of spontaneous ocular recurrence. In three experiments reported here, the normal pattern of recurrence was modified by manipulation of the trigeminal nerve and ganglion. Temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals significantly decreased the number of ocular HSV isolations obtained during the 20 weeks immediately following surgery. Stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. In chronically infected animals, stereotaxic stimulation of the trigeminal ganglion caused a marked increase in positive cultures within 2 days. These studies provide additional evidence for the theory that the reservoir for latent ocular HSV in rabbits is the trigeminal ganglion. Moreover, the studies suggest that the transmission of latent HSV from the trigeminal ganglion to its infectious form in the peripheral tissues involves the trigeminal nerve. We have shown that mechanical and stereotaxic stimulation of the trigeminal ganglion is a reliable and rapid means of precipitating peripheral ocular shedding of HSV on command, a finding which should prove most productive in future research.