Purpose: To determine the influence of nicotine upon the release of interleukin-6 (IL-6) from human periodontal ligament fibroblasts (HPLF). Methods and Materials: The HPLF were exposed to nicotine concentrations of 125 to 1500 ėg/ml for 24 hours (h). IL-6 release and cell growth were determined after exposure to the different nicotine concentrations after 24 hours. IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA). Cell counts were determined with a Coulter counter. Results: HPLF cell counts were significantly higher than untreated cells after nicotine exposure of 375 ėg/ml and significantly lower than untreated cells for cells treated with 1500 ėg/ml nicotine. After 24 h of cell exposure to nicotine concentrations of 250 and 375 ėg/ml, HPLF release of IL-6 per cell was significantly higher than that of untreated HPLF. HPLF treated with 1500 ėg/ml, nicotine released significantly less IL-6 per cell than did untreated cells. Conclusions: These results indicate that nicotine can increase IL-6 release from HPLF.