We have observed a marked species specificity in the in vivo antitumor, shock-inducing and Interleukin-6 (IL-6)-inducing activities of human recombinant TNF (hrTNF) versus murine rTNF (mrTNF) in mouse models. We also have observed that this species specificity can be abolished when synergistic factors are co-administered. We now present data showing that the profiles of induced IL-6 and TNF after lethal and non-lethal doses of endotoxin are different. These results are discussed in the context of a model of dual signalling for the induction of the major post-endotoxin phenomena that takes into consideration the involvement of Interleukin-1 (IL-1) in the in vivo actions of TNF.