Human peripheral blood monocytes can produce interleukin-1 (IL-1) beta following the addition of picogram amounts of bacterial lipopolysaccharides (LPS). The activation of IL-1 production by these cells can be mimicked by manipulation of specific biochemical pathways which appear to be independent of, and synergistic with, the pathways activated by LPS. Such pathways may be used by other physiological systems to modulate the production of IL-1. Both negative and positive modulation of IL-1 production can be described. Selected chemical antagonists of the arachidonic acid cascade have been shown to inhibit IL-1 production. The activity of such compounds does not appear to be related to their activity as inhibitors of cyclooxygenase or lipooxygenase enzymes or to activity as antioxidants. The intracellular form of IL-1 beta is limited to the precursor, which is found cytoplasmically. The release of IL-1 by activated cells appears to be regulated, in part, by the integrity of the microtubule system of the cells.