Several of the biological effects of bacterial lipopolysaccharide (LPS) can be induced by the lipid A part of the molecule. Here we show that in human peripheral blood monocytes, synthetic E. coli lipid A is as effective as the whole LPS molecule in inducing the production of interleukin 1 (IL-1) bioactivity which remains associated to the cells (i.e. IL-1 alpha). In contrast, LPS- but not lipid A-stimulated cells released the bioactive IL-1 produced into the culture supernatant (mainly IL-1 beta). Northern blotting analysis demonstrated, however, that LPS and lipid A are equally effective in inducing the accumulation of IL-1 alpha and IL-1 beta mRNA. These data support the hypothesis that induction of IL-1 biosynthesis and activation of the secretory mechanism for IL-1 are independent phenomena.