Elevation of cAMP has been considered to be an important downregulative signal in the production ofinterieukin-1(IL-1). This study demonstrates that this phenomenon is dependent on the signal used to activate the IL-1 production. The IL-1β production of lipopolysaccharide activated human monocytes was readily inhibited by dibutyryl cAMP. This took place without a significant change in the steady-state levels of IL-1β mRNA. By contrast, in PMA activated monocytes 100 μM dibutyryl cAMP increased in IL-1β production ca. 4-fold. The steady-statelevels of IL-1β mRNA were also simultaneously increased.