We evaluated the relationship between plasma concentrations of the renal hormone 1,25-(OH)2-vitamin D and net intestinal absorption of Ca, PO4, and Mg in vitamin D-replete patients eating similar diets, who had undetectable, normal or elevated plasma 1,25-(OH)2-D levels, Net intestinal Ca absorption was positively correlated to plasma 1,25-(OH)2-D concentrations: percentage dietary Ca absorbed = 10 + 0.17 x plasma total 1,25-(OH)2-3, pmole/liter, r = + 0.58; P less than 0.001. By contrast, there was no significant correlation between PO4 or Mg absorption and plasma 1,25-(OH)2-D concentrations. Moreover, significant quantities of PO4 and Mg were absorbed in the absence of detectable plasma 1,25-(OH)2-D. We conclude that net intestinal Ca absorption is critically dependent upon the availability of the renal hormone 1,25-(OH)2-D in vitamin D-replete humans when dietary Ca intake is normal. By contrast, other factors must play a dominant role in regulating net intestinal PO4 and Mg absorption.