Gram-negative bacteria recovered from necrotic pulps of teeth with periapical lesions have been shown to promote bone resorption through the effects of their lipopolysaccharide (LPS). Recently, it was shown that microflora of root-filled teeth with persisting periapical lesions consisted mainly of single species of Gram-positive bacteria. But Gram-positive bacteria do not contain LPS and their role in the development of periapical lesions is not clearly understood. The purpose of this study was to evaluate the effects of muramyl dipeptide (MDP), a cell wall component of both Gram-negative and Gram-positive bacteria, on cytokine release from monocytes. Human monocyte cultures were treated with MDP or LPS and interleukin-1 beta, and tumor necrosis factor-alpha levels in the supernatants were estimated. MDP and LPS stimulated cytokine release, but the effect of MDP was significantly less than that of LPS.