In order to make clear the characteristic biological properties of IL-1 alpha, its protective capabilities on bacteria-induced and LPS-induced lethality were compared with other BRMs in BALB/c mice. Pretreatment with IL-1 alpha (i.p., s.c.) or OK-432 (i.p.), could protect mice from the lethality of a K. pneumoniae infection (i.p.), and pretreatment with IL-1 alpha or TNF alpha could protect mice from LPS (i.p.) lethality. IL-1 alpha could protect mice from both bacteria- and LPS-induced lethality. There was no difference in serum corticosterone levels after the LPS injection between the IL-1 alpha pretreated and untreated groups. However, a more rapid clearance of LPS from the serum and a stronger LPS-neutralizing activity in serum were observed with the LAL assay in IL-1 alpha pretreated mice than in untreated mice. The enhanced LPS-clearance was suggested to be partly responsible for the increased protection against LPS-lethality. IL-1 alpha was indicated to be a unique BRM and to become a useful tool for the prevention of life-threatening bacterial infections and subsequent endotoxin shock.