Mice injected i.p. with polyethylene glycols (PEG) 20 min prior to head and neck X irradiation with 1650 rad showed improved survival, increased food and water consumption, and retention of body weight compared with irradiated controls. The LD 50 15 for PEG-treated mice was 1900 ± 108 rad compared to 1527 ± 56 for the controls. PEG of molecular weights 200, 400, and 600 afforded significant levels of radioprotection; PEG of molecular weights 1000, 1450, 4000, and 20,000 when given at maximum tolerated doses (∼0.5 LD 50) did not. The degree of radioprotection by PEG with molecular 400 given 20 min before irradiation increased with dose up to the maximum tolerated dose of 6.4 g/Kg. Significant, but lower, levels of radioprotection were observed when the PEG was given 5 min after irradiation. Mice injected i.p. with PEG, cystamine, 5-thioglucose, chlorpromazine, polyethylene glycol monomethyl ether or polyvinylpyrrolidone all had comparable survival levels. Polypropylene glycol, polyethylene glycol diacrylate, and polycaprolactonediol were more toxic than PEG and showed no radioprotection.