The properties of ideal retrograde filling materials include the ability to seal the root canal system in three dimensions and well tolerated by periradicular tissues. Biocompatibility testing has been done mainly with cytotoxicity tests using cell culture. Little attention has been paid to the potential adverse influence on the inflammatory and immune reaction in the periapical tissue. The purpose of this study was to investigate the effects of retrograde filling materials on human mononuclear cells in vitro. Freshly mixed and set specimens from six materials (Z100, Tetric Ceram, Fuji II, Fuji II LC, F2000, Compoglass Flow, and ZOE) were eluated with cell culture medium for 24 hours. Cytotoxic effects of these extracts were evaluated by determining cell viability and enzyme activity using MTT and lactate dehydrogenase (LD). The production of inflammatoy bone resorptive cytokine, TNF-${alpha}$ was measured from human peripheral blood mononuclear cells (PBMC) exposed to the extracts by means of Endogen Human TNF-${alpha}$ ELISA kit (Wobrun, MA, U.S.A.). Eluates and diluted (1 : 10) eluates with cell culture medium from freshly mixed Fuji IT had cytotoxic effects on mononuclear cells using MTT and LD. However, eluates from set Fuji II were not cytotoxic. Eluates form set ZOE exhibited cytotoxicity with LD test. TNF-${alpha}$ levels were high in eluates from freshly mixed Fuji II and Z100. Diluted eluates from freshly mixed Z100 and F2000 stimulated the production of TNF-${alpha}$. However, there were no significant difference in TNF-${alpha}$ levels compared to controls. These results indicate that some materials could possibly stimulate bone resorption in the periapical tissue by means of the production of bone resorptive cytokine.