In order to determine whether the bacterial bone resorbing agents lipopolysaccharide (LPS) and muramyl dipeptide (MDP) interact with osteoblasts, their effect on the synthesis of collagenase and tissue inhibitor or metalloproteinases (TIMP) from monolayer cultures of mouse osteoblast-like cells was investigated. All concentrations of LPS (0.1, 1.0 and 10.0 micrograms/ml) significantly stimulated collagenase levels compared to unstimulated controls. This suggests that LPS, like hormonal stimulators of bone resorption, interacts with osteoblasts. In contrast, MDP (0.01, 0.1 and 1 microM) did not significantly stimulate collagenase or TIMP levels, indicating that MDP may not interact with osteoblasts. Possible alternative mechanisms of MDP-mediated bone resorption are discussed.