Repeated intraperitoneal doses of preformed interferon and a single intraperitoneal injection of polyacrylic acid were shown to protect newborn mice from lethal infection with vesicular stomatitis virus. Both survival time and number of surviving mice were considerably increased by the injections. The antiviral activity of interferon and polyacrylic acid was inversely proportional to the dose of challenge virus. Nearly 100% of the mice treated with interferon survived a nearly 100% lethal infection (16 LD50). Polyacrylic acid diminished the mortality rate by 50 %. It is concluded that polyacrylic acid induces good host resistance to viruses and may be suitable in the prophylaxis of virus infections in vivo. © 1968.