Germ-free ICR mice monoassociated with Bifidobacterium longum (GB mice) lived longer than non-treated germ-free (GF) mice after intragastric or intravenous (i.v.) administration of a high dose of viable E. coli, or i.v. injection of endotoxin. The number of viable E. coli and the endotoxin level in various organs at 24 hr post - injection were significantly lower in GB than GF mice. Antilethal activity was not elicited by the feeding of heat-killed B. longum. The antilethal effect was observed 3, but not less than 2, weeks after the association of B. longum. Furthermore, the effect was not observed when GF-athymic nude mice (BALB/c background) were used. After intragastric administration of a sublethal dose, the number of viable E. coliin organs of GB mice decreased to an undetectable level within 7 days, while the organisms were persistently isolated in GF mice. In both groups, many (109 v.c./g) E. coli persisted in the intestine. These results suggest that B. longum organisms monoassociated with GF mice generate systemic resistance to the invading E. coli, and increase the resistance to the lethal activity of endotoxin.