Activated macrophages synthesize and release the potent polypeptides, interleukin-1 (IL-1) and tumor necrosis factor (TNF). In an effort to identify the cellular signals which control cytokine production by activated macrophages, we have developed an in vitro model employing the human THP-1 cell line. In the present study, THP-1 cells "primed" by 1.6 microM phorbol 12-myristate-13-acetate (TPA) for 4 hr demonstrated a dose- and time-dependent release of IL-1 beta and TNF upon activation by 20 micrograms/ml LPS. BSA/anti-BSA-coated latex beads were also a potent stimulus for IL-1 beta secretion. Moreover, the combination of a suboptimal concentration of LPS (200 ng/ml) plus interferon-gamma (0.03-333 U/ml) greatly enhanced IL-1 beta production. Resting THP-1 monocytes not "primed" by TPA did not secrete IL-1 beta or TNF. These distinct patterns of cytokine production may be related to the developmental stages of macrophage activation.