Previous balance studies have shown that fractional calcium absorption is increased by a low and reduced by a high calcium diet. The present studies were done to determine which segment of the small intestine is most sensitive to alterations in dietary calcium, and to see if dietary calcium intake has an effect on the intestinal absorption of another divalent cation, magnesium. Absorption was measured during constant perfusion of 30-cm segments of jejunum and ileum of normal subjects after 4 or 8 wk of a high (1,900 mg/d) or a low (20 mg/d) calcium diet. We found that calcium absorption rate was higher when subjects had been on a low than when they had been on a high calcium diet; the ileum responded more rapidly and more completely than the jejunum. Similar results were obtained with magnesium, but only the difference in the ileum was statistically significant. Sodium and xylose absorption were not influenced by dietary calcium intake. The serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were higher on the low than on the high calcium diet. We conclude that the ileum is more sensitive than the jejunum to changes in dietary calcium intake, and that ileal adaptation probably plays a major role in protecting the body against a deficiency or excess of body calcium that otherwise would occur when dietary calcium is abnormally low or high. Calcium intake influences ileal magnesium absorption in a similar fashion; it is not known whether or not this serves a protective function. Our data are compatible with the concept that adaptation to dietary calcium intake is mediated by changes in the serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D.