We have studied the peculiarities of the nonlinear compartmental model for human Sr metabolism developed earlier [see companion paper: Staub JF, Foos E, Courtin B, Jochemsen R and Perault-Staub AM. Am J Physiol (this issue)], including its physiological reliability within the context of Sr-Ca similarity/dissimilarity. We found it to be relevant to Ca metabolism, except for discrimination against Sr relative to Ca at urinary and intestinal levels. There are 3 main findings: First, the saturable part of intestinal absorption, shared by Sr and Ca, does not seem responsible for the discrimination of the transcellular pathway. Second, although there is little discrimination in bone, the physicochemical behaviors of Sr and Ca at the bone surface differ, at least quantitatively. Third, Sr behaves not only as a "tracer" for Ca metabolic pathways but, under non steady state conditions, can also reveal self-regulatory processes. It is suggested that they depend on Ca²⁺(cation)-sensing receptors apparently more sensitive to Sr than to Ca. Acting on GI and osteoblast lineage cells, these slow processes might contribute to adaptive rather than homeostatic regulation of Ca metabolism. Understanding these features could help clarify the pharmacological and therapeutic effects of oral Sr.