Aim of this study was to investigate whether osteoclast activity changes as a consequence of even mild physiological perturbation of plasma calcium as such induced by an oral calcium load. Osteoclast activity was determined indirectly by measuring, in spot urines at two and four hours after oral calcium load, the urinary excretion of hydroxylysylpyridinoline (Pyr), deoxylysylpyridinoline (D-Pyr), hydroxyproline (Hyp) and galactosyl-hydroxylysine (GHyl). The occurrence of the metabolic perturbation of plasma calcium homeostasis was assessed by measuring three indexes: i.e. calcemic response, PTH reduction and calciuric response at times following oral calcium loading. A significant fall of urinary D-Pyr and Pyr followed the perturbation of calcium homeostasis induced by the oral calcium load in two groups of healthy young adult and postmenopausal women. The highest mean percent reduction was observed for D-Pyr and was quantitatively similar in the two groups. Since urinary D-Pyr is the most specific bone resorption marker, it may be inferred that the perturbation of plasma calcium homeostasis induced by an oral calcium load is able to acutely inhibit osteoclast activity. This supports the view that osteoclasts are involved in the short-term error correction of plasma calcium.