Addition of interferon to ineffective rabies virus vaccines by the local injection of either exogenous interferon or a potent interferon inducer (a complex of polyriboinosinic-polyribocytidylic acid containing poly-L-lysine and carboxymethylcellulose) into the footpads of mice previously challenged with rabies virus dramatically reduced the mortality rate. A significant reduction in mortality rate was also noted when the interferon system was administered to rhesus monkeys, but only when treatment was given 6 hr after challenge with rabies virus. Since the monkeys were given an overwhelming challenge of virus, the treatment had to be given quickly to obtain results comparable to those in mice.