AbstractIonizing radiation increases the recipient's susceptibility to local and systemic infection by endogenous and exogenous microorganisms. Most infections involve fatal Gram-negative septicemia, but those associated with trauma may be polymicrobial. The use of quinolone antimicrobial agents in the treatment of these infections in irradiated mice is reviewed. Quinolones were effective in controlling systemic endogenous Gram-negative infection following irradiation. Supplementation of quinolone therapy with penicillin prevented treatment failures due toStreptococci, and increased survival. Quinolones were found also to be effective in management of systemic exogenous infections due to orally ingestedKlebsiella pneumoniaeandPseudomonas aeruginosa. A 21-day course of therapy ofK. penumoniaeinfection was superior to a 7-day therapy. The effectiveness of quinolones in the management of these infections may be attributed to local inhibition of the offending organism's growth within the gut lumen, while preserving the anaerobic gut flora and their systemic antibacterial activity. Administration of agents effective against anaerobic bacteria may be required for the management of polymicrobial infections. Supplementing antianaerobic therapy with a quinolone can control the Gram-negative bacterial component of the infection and prevent Enterobacteriaceae translocation and mortality. The availability of an oral, as well as parenteral, route of administration, the advantage of achieving selective inhibition of potential pathogens in the gut, and the ability to treat systemic infection make the quinolones promising agents for the therapy of endogenous and exogenous infections after irradiation.