A rhesus monkey housed in the New England Regional Primate Research Center for more than 4 yr died after an illness of 19 da. Clinical signs included central nervous system involvement and ulcers on the labial mucosa. Microscopically, the cause of death was established as multiple cerebral infarction. Lesions characteristic of herpesvirus infections were not present in the brain nor in any other tissue; however, Herpesvirus simiae was isolated from oral and anal swabs as well as from tongue and lung tissue. Inoculation of this agent in H simiae antibody negative rhesus monkeys resulted in infection, as indicated by virus isolation, serologic conversion, conjunctivitis, and development of ulcers at the mucoepithelial border, but fatal infection did not develop.