Injected recombinant interleukin-6 (IL-6), tumour necrosis factor (TNF) and IL-1 all protect mice against experimental infection with Listeria monocytogenes. We have therefore investigated the interaction of these cytokines during infection. Treatment with recombinant (r)IL-6 enhanced TNF production by spleen cells during the first 2 days of infection. Anti-TNF antibody could totally abolish the protective effect of rIL-6, while the optimal protective function of TNF could not be achieved when IL-6 was neutralized by anti-IL-6 antibody. IL-1 induced a high level of IL-6 in the serum a short time after its administration, and neutralization of IL-6 totally abolished the protective function of rIL-1. The results thus provide further evidence for the complexity of cytokine interaction.