Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-fl-D-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2'-deoxyuridine, distamycin A, and N-ethylisatin 13-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group.Equine abortion virus (EAV) or equine rhinopneumonitis virus is a member of the herpesvirus group. Doll and co-workers (5) first adapted EAV to Syrian hamsters, and Randall and Bracken (15) described the growth cycle of the virus in hamsters characterized by a viremia and fulminating hepatitis followed by death.In the present study, the protective effect of inducers of interferon and selected inhibitors of deoxyribonucleic acid (DNA) viruses was evaluated in hamsters experimentally infected with EAV. Serum interferon levels in hamsters injected with interferon inducers were also determined. triturated as a 10% suspension in phosphate-buffered saline (PBS) containing 2% bovine serum albumin, sealed in ampoules, and stored at -60 C. For most studies, hamsters under light ether anaesthesia were infected by ip injection with 1 to 13 LD50 of virus, and they usually died in 3 to 7 days. Larger doses of virus killed animals as early as 24 to 48 hr after injection.The Indiana strain of vesicular stomatitis virus (VSV) was obtained from S. Baron, National Institutes of Health, Bethesda, Md. A stock virus was propagated in L-929 cells and stored at -60 C.Hamsters