The regulation of interleukin 6 (IL-6) is dependent on many factors that include numerous stimuli such as lipopolysaccharide (LPS), viruses, and other cytokines. These studies demonstrate the ability of interferon-gamma (IFN-gamma) to significantly enhance IL-6 mRNA and protein production in LPS-stimulated monocytes and THP-1 cells. IL-6 protein production was increased sevenfold in LPS-stimulated cells with the addition of IFN-gamma. IL-6 mRNA production was increased in a dose-dependent fashion up to 15-fold in LPS-stimulated cells with the addition of IFN-gamma. The enhanced production of IL-6 mRNA that occurs with the addition of IFN-gamma to LPS-stimulated monocytic cells was due to increased transcription of IL-6 mRNA. The ability of IFN-gamma to enhance IL-6 production may play an important role in many inflammatory processes.