We measured net calcium absorption and the calcium content of the digestive glands secretions in people with widely different serum concentrations of 1,25 dihydroxy vitamin D (hereafter referred to a 1,25-D). Patients with end stage renal disease on hemodialysis served as a model of human 1,25-D deficiency; they were also studied when they had abnormally high serum 1,25-D concentrations as a result of short periods of treatment with exogenous 1,25-D. Normal subjects were studied for comparison. The amount of calcium secreted into the duodenum by the digestive glands was found to be trivial compared to the calcium content of normal or even low calcium meals; therefore, values for net and true net calcium absorption differed only slightly. There was a linear correlation between true net calcium absorption and serum 1,25-D concentration. By extrapolating the short distance to a zero value for serum 1,25-D, D-independent true net calcium absorption was estimated. By subtracting D independent from true net calcium absorption, values for D-dependent absorption were obtained. For a given level of meal calcium intake, D-dependent calcium absorption was found to be directly proportional to serum 1,25-D concentration. At any given value for serum 1,25-D, absorption via the D-dependent mechanism was approximately the same with a low (120 mg) calcium meal as it was when meal calcium intake was increased to 300 mg. We interpret this to mean that the D-dependent mechanism is saturated or nearly saturated by low calcium meals. The D-independent absorption/secretion mechanism resulted in secretion (a loss of body calcium in the feces) when intake was low (120 mg per meal) and absorption when intake was normal. All of the increment in calcium absorption that occurs when low or normal calcium meals are supplemented with extra calcium is mediated by the D-independent mechanism.