Since herpes simplex virus (HSV) can cause persistent infection of autonomic ganglia of both humans and experimentally infected animals, we followed the pattern of eye disease and viral growth after HSV inoculation of one superior cervical ganglion in rabbits. Of 27 inoculated animals, eye disease or detectable virus developed in 18. Anterior uveitis was the most common clinical manifestation (94%), but conjunctivitis and dendritic keratitis were also frequent (60%). All 12 uveal-retinal specimens tested and five of seven ipsilateral superior cervical ganglia had detectable virus. If recurrent herpetic iritis in humans is associated with persistent infection of the superior cervical ganglion, autonomic mediators might trigger episodes of virus shedding. In patients with herpetic iritis, then, the use of epinephrine and other adrenergic agonists or antagonists should be avoided.