Milk fever is the clinical disease associated with severe hypocalcemia in dairy cows. In this experiment, we tested the hypothesis that calcium homeostasis is a result of a decreased concentration of receptors for 1,25-dihydroxyvitamin D in the tissues of cows that develop milk fever. Samples of colon mucosa were obtained for analysis of vitamin D receptor concentration in a longitudinal study of Jersey cows during the 2 wk before and after parturition. In the first study, 21 cows fed an alfalfa hay diet were biopsied every 3rd d from 2 wk before to 2 wk after calving. The concentration of vitamin D receptor in the colon during late gestation was three- to fourfold higher than the concentration of vitamin D receptor in the colon mucosa in nonpregnant cows (90 +/- 8 vs. 26 +/- 5 fmol/mg of protein). At parturition, colon concentration of vitamin D receptor decreased to 66 +/- 7.5 fmol/mg of protein. During early lactation, concentrations of vitamin D receptor in the colon were similar to precalving concentrations. There was no significant difference of concentrations of vitamin D receptor in the colon prior to calving, at calving, or in early lactation between cows that did develop milk fever and those that did not. Results were similar in a second study, in which 7 cows were fed a high cation alfalfa diet, and 6 cows were fed the same diet with anionic salts added. Those data do not support the hypothesis that decreased concentrations of vitamin D receptor prior to calving is a causative factor of milk fever within the Jersey breed. However, a decline of concentrations of vitamin D receptor in tissue at calving may reduce the ability of all cows to respond to the calcium demands of lactation.