Neonatal mice within 24 h of birth were highly susceptible to infection of Listeria monocytogenes. The 50% lethal dose of bacterial cells for neonates and adult mice was 6.3 X 10(1) CFU and 3.2 x 10(6) CFU, respectively. A single intraperitoneal injection of recombinant murine interferon-gamma (rMuIFN-gamma) protected neonates from the simultaneous challenge with a lethal dose of L. monocytogenes. The protection of rMuIFN-gamma was consistently observed in neonates at doses more than 4 X 10(2) IU (0.1 micrograms protein) per mouse. The bacterial growth in the spleens and livers of neonates treated with rMuIFN-gamma was significantly suppressed in comparison with that in the untreated neonates. Furthermore, survived neonates from the infection with L. monocytogenes showed an acquired resistance against the intravenous injection of lethal dose of L. monocytogenes 4 weeks after the primary infection, and this resistance significantly increased in mice that had been treated with rMuIFN-gamma. In addition to rMuIFN-gamma, recombinant human interleukin-1 beta and recombinant human tumor necrosis factor -alpha were also effective on rescue from the lethal infection with Listeria monocytogenes in neonatal mice, but the effect was seen only in the limited doses. On the other hand, recombinant murine IFN-beta and recombinant human IL-2 were not effective at all. These results suggest that rMuIFN-gamma rather than other cytokines might endow neonatal mice with the enhanced antilisterial resistance involving macrophages and T lymphocytes.