Sublethal quantitiesof homologous and heterologous influenza virus, mumps virus, and Newcastle disease virus injected intravenously in mice produced a state of resistance to the toxic effects of large quantities of intravenously injected PR-8 influenza A virus. Virus heated sufficiently to destroy infectivity was less effective in inducing resistance than was fully active virus; destruction of hemag-glutinin caused complete loss of resistance inducing activity. Injection of sublethal doses of virus was followed by a lag period, which varied with the virus injected, before resistance became demonstrable, and resistance waned after 3-4 days. No increase in resistance to influenza toxicity was demonstrable after pre-challenge injection of feline penumonitis virus, Rickettsia prowazeki, or typhoid vaccine. A preparation of receptor destroying enzyme (RDE) was effective in inducing increased resistance but its effect could not be attributed to its capacity for destruction of muco-protein receptors since heat destruction of this activity did not completely destroy its resistance-inducing effect.