Pulpal disease is intimately associated with the immune system's response to bacteria products. Clinical pathology is mediated in part by the production of pyrogenic cytokines, especially interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6. Methyl mercaptan (CH3SH), a volatile sulfur compound produced by anaerobic Gram-negative bacteria, has been shown to contribute to the production of IL-1 by human mononuclear cells. In this report, we investigated the production of IL-1, TNF-alpha, and IL-6 by human pulp fibroblasts when stimulated for various periods of time with lipopolysaccharide (LPS) with or without the presence of CH3SH. We found that LPS and CH3SH had no effect on the production of IL-1 or TNF-alpha. However, LPS stimulated IL-6 production, and this production was augmented when CH3SH was present. We conclude that the volatile sulfur compound CH3SH plays a role in activation and modulation of the immune response through its role in production of IL-6.