In rapidly growing neonatal rats, the intestine is insensitive to vitamin D, and Ca absorption is solely mediated through a non-energy-dependent process. Changes in Ca absorption associated with pregnancy and lactation are qualitatively similar in vitamin D-replete and vitamin D-deplete rats. Moreover, in vivo studies in man and the rat have demonstrated that the bulk of Ca absorption is accomplished in the ileum, a segment with limited capacity for active Ca absorption and is relatively insensitive to the action of 1,25-dihydroxyvitamin D. In patients with intestinal bypass operations the degree of Ca malabsorption and bone mineral loss is proportional to the length of ileum, not duodenum or proximal intestine, removed. Bile salts and lactose are examples of agents which can augment vitamin D-independent ileal Ca absorption through the intercellular pathway.