Convincing evidence for the stimulatory action of 1,25-dihydroxyvitamin D (1,25(OH2)D) on transcellular absorption of calcium (Ca) and inorganic phosphate (P) has led to the consensus that this hormone is the major regulator of Ca and P absorption. Careful review of the literature, however, suggests important regulation of Ca and P absorption by factors and agents other than those mediated by vitamin D. Thus, in rapidly growing neonatal rats, the intestine is insensitive to vitamin D and Ca absorption is entirely mediated through passive mechanisms. Patterns of change in Ca absorption associated with pregnancy and lactation are identical in vitamin D-replete and vitamin D-deplete rats. The presence of active Ca and P absorption in young, growing rats rigidly deprived of vitamin D and of active Ca and P secretion in mature rats optimally replete with vitamin D, also suggests the participation of non-vitamin D factors in the regulation of intestinal Ca and P absorption. The possibility that Ca and P in the peri-enterocyte environment may regulate their own absorption is discussed. Kinetic analysis of 1,25(OH2)D-induced transport mechanisms indicates that saturation would occur at low substrate concentrations, thus raising the question whether these mechanisms would have major regulatory roles under normal dietary conditions. There is also suggestive evidence indicating that even under conditions of low dietary Ca or P intake, the adaptive changes in intestinal absorption may not be mediated by vitamin D alone. Bile salts, lactose and prolactin are discussed as examples of agents which can stimulate Ca and/or P absorption through vitamin D-independent mechanisms.