A model of Strontium (Sr) metabolism was developed by using plasma and urinary Sr kinetic data obtained in groups of postmenopausal women receiving 4 different oral Sr administration doses and collected during both the Sr administration period (25 days) and additional 28 days following cessation of treatment. A nonlinear compartmental formalism appropriate to study non-steady state kinetics and allowing dissociation between variables pertaining to Sr metabolism itself (system [1]) and those indirectly operating on it (system [2]) was used. At each stage of model development, the dose-dependent model response was fitted to the 4 sets of data considered simultaneously (one set per dose). A 7-compartment model with internal Sr distribution, and intestinal, urinary and bone metabolic pathways was selected. It includes two kinds of nonlinearities: the first ones accounting for saturable intestinal and bone processes behave as intrinsic nonlinearities since they are directly dependent on Sr. The others, called extrinsic nonlinearities (dependent on system [2]), suggest the cooperative involvement of plasma Sr changes in modulating some intestinal and bone mineral metabolic pathways. With the set of identified parameter values, the initial steady state model predictions are relevant to known physiology, and some peculiarities of model behavior for long-term Sr administration were simulated. The very physiological significance of this model shall be analyzed in the companion paper (Staub JF, Foos E, Courtin B, Jochemsen R and Perault-Staub AM. Am J Physiol (this issue)), mainly concerned with its applicability to Ca metabolism.