There is increasing evidence that antiserum to LPS can reduce the morbidity and mortality of Gram-negative bacterial infections. We report that antiserum to S. typhimurium SL 1102 (Re mutant strain) has excellent cross-protective activity. Antisera to these bacteria and to their Re-LPS were prepared in rabbits immunized with heat-killed bacterial cells and with Re-LPS preparations. Re-LPS antibody titers were tested by immune hemagglutination (IHA) and by ELISA. These antisera were found to be capable of protecting ICR mice against lethal challenge with S-type S. typhimurium 50014 (100 LD50), E. coli 0111:B4 (32 LD50), Pseudomonas aeruginosa (8 LD50) and Klebsiella pneumonia (16 LD50). We used gastric mucin (5%) as a virulence enhancing agent for the bacterial challenges. The IHA titer of antibody to the homologous strain proved to be much higher than that of other strains. Protection by the sera was 75-100%, 25% and 0% when injected 24, 48 or 72 h before the challenge, respectively. The survival rate was more than 50% when the antiserum was injected 5-7 h after challenge with a ten-fold or higher lethal dose. No protection was observed against such high challenge when the serum was injected later. According to these results, Re-LPS antiserum provides better protection than S-type specific antisera.