A physical model of calcium absorption was developed from analysis of data obtained on 23 subjects, including 13 patients having a variety of abnormalities of calcium metabolism. The model was tested and found consistent in all subjects studied. This technique provides a quantitative description of the rate of entry of oral dose of (47)Ca into the circulation as a function of time by analysis of serum or forearm radioactivity in response to intravenous and oral administration of (47)Ca. The kinetics of the absorption process as proposed by the model are characterized by an initial delay phase of 15-20 min, by a maximal rate of absorption at 40-60 min after ingestion, and by 95% completion of the absorption within 2(1/2) hr. Partial identification of the physiological counterparts of the model was possible by introduction of the isotope at various levels of the gut. Although the region of the duodenum was found to have the greatest rate of absorption per unit length in normal subjects, it was least responsive to stimulation by parathyroid hormone and suppression by calcium loading. Furthermore, the response of the gut to parathyroid hormone was delayed, whereas the suppression of absorption by intravenous or oral calcium loading was rapid and dramatic. The implications of these observations are discussed.