Objective. To study the in vitro effects of human haptoglobin (Hp) on bone resorption and prostanoid formation. Methods. Parietal bones were dissected out from neonatal mice that had been injected with Ca-45, and were cultured in chemically defined medium with or without test substances. Bone resorption was assessed by analysis of Ca-45 release. Prostanoid formation was quantified by analysis of the amount of prostaglandin E2 (PGE2) in culture medium. Results. Hp phenotype 2-1, in quantities greater-than-or-equal-to 0.17 mg/ml, stimulated the release of Ca-45 and the biosynthesis of PGE2, in a time- and dose-dependent manner. Hp-induced PGE2 formation was abolished by indomethacin and flurbiprofen, whereas the stimulation of Ca-45 release was only partially reduced. Conclusion. These observations suggest that the acute-phase reactant Hp may contribute, by a humoral mechanism, to the bone resorption seen in chronic inflammatory processes.