In the cytokine cascade, a central position is occupied by that molecule known as "cachectin" or "tumor necrosis factor," because this molecule, more than any other, has been shown to mediate the biologic effects of LPS, and to provoke a state of wasting very similar to that observed in cancer cachexia. The history of the isolation of this factor is instructive, because it illustrates the fact that a single mediator may transduce a broad spectrum of biologic effects, and may thus present itself to investigators interested in very disparate phenomena.