A circumscribed natural outbreak of a highly fatal disease of deer, which we have designated epizootic hemorrhagic disease (EHD), has been studied. The disease has proven readily transmissible in deer but not in other experimental or domestic animals tested, nor in embryonating eggs or deer kidney cell cultures. The causative agent is a virus which is readily filterable and is capable of storage, either frozen or in glycerol, for relatively long periods of time. It produces a solid immunity in the few animals that survive and the blood sera of such convalescent animals contain virus-neutralizing antibodies. The disease is one in which large and small hemorrhages occur in both the viscera and skeletal structures of the body, as well as in the subcutaneous tissues. It is probably the same as one known popularly in the southeastern United States as "black tongue" of deer. It is unrelated to epidemic hemorrhagic fever of man or to the disease caused in horses by the equine arteritis virus. At least two serologically different types of EHD virus exist. The New Jersey strain is of greater lethality for experimental deer than the serologically different one obtained from an outbreak that occurred in South Dakota a year after the New Jersey epizootic.

A naturally occurring cutaneous fibroma of deer has proven to be experimentally transmissible in deer. The causative agent is a virus that is readily alterable through Berkefeld N candles and that survives in fibroma tissue for at least as long as 27 months in glycerol-saline at –20°C. The experimentally produced deer fibroma has an incubation period of about 7 weeks, a very slow rate of growth, and a high regression rate.

The New Jersey strain of EHD virus has been propagated in newborn Swiss mice by the intracerebral route and is regularly lethal beyond the first serial mouse passage. A complement-fixing antigen prepared from the brains of infected mice reacts positively with the sera of deer recovered from infection with either the New Jersey or South Dakota strain of virus, but not with the serum of normal deer. The mouse-passaged virus induced an inapparent infection in an experimental deer. The virus can also be grown serially in HeLa cell culture and induces a characteristic cytopathic effect. It is neutralizable in such cultures to high titer by the sera of deer recovered from EHD (New Jersey strain) and to lower titer by the serum of a deer recovered from EHD (South Dakota strain). Normal deer serum does not neutralize the virus in tissue culture. The HeLa cell-passaged virus induced typical lethal EHD in an experimental deer and virus could be recovered from most of the tissues of this animal in HeLa cell culture. An unexplained prozone of inhibition of cytopathogenicity at low dilutions was observed in cultures of some of the organs. The fact that EHD virus exhibited a limited sensitivity to sodium desoxycholate suggests that it may belong in the arbor virus group.

Serial passage through the brains of newborn mice markedly attenuates the New Jersey strain of EHD virus. Deer inoculated with this attenuated virus show no clinical evidence of illness, but do develop virus-neutralizing antibodies in their sera. They also become solidly immune to infection with the regularly fatal unattenuated virus.