Intcrlcukin (IL-1) production in human monocyles was examined in response to stimulation by different moleculai forms of bacterial lipopolysacchandes (LPS), recombinant human gamma interferon (IFN-γ) and vanous forms ol immune complexes with or without complement. Stimulation of IL-1 production by LPS was enhanced by the presence of the 2-keto-3-deoxyoctonate (KDO) moiety as well as by diphosphoryl lipid A. IFN-γ alone did not induce IL-1 production but enhanced the stimulatory effects of LPS. Various forms of immune complexes, in the absence of detectable LPS contamination and of complement, failed to stimulate IL-1 production. Complement fixation by immune complex precipitates led to induction of IL-1 synthesis and secretion. Monocytes cultured on adherent immune complexes produced a specific IL-1 inhibitor