Fetal mineralization appears to be driven by the pregnancyinduced stimulation of intestinal Ca absorption. We thus hypothesized that mineralization would be impaired in fetuses of mice that lack the vitamin D receptor (VDR). Here we report on the maternal response to pregnancy, and the fetal mineralization, in mice with a homozygous disruption of the VDR gene (VDRϪ/Ϫ) mated with wild-type (wt) males. We found that VDRϪ/Ϫ mice show mild hypocalcemia, clear rickets and osteomalacia on bone histomorphometry, lower cortical bone density on quantitative tomography, and reduced concentrations of calbindin-D 9k ) in duodenal mucosa and kidney. The skeletal response to pregnancy was comparable in wt and VDRϪ/Ϫ mice; duodenal CaBP-D 9k concentrations increased during pregnancy in VDRϪ/Ϫ as in wt mice, but remained 40% lower than in wt mice. We confirmed our hypothesis that mineralization is defective in d18.5 VDRϩ/Ϫ fetuses of VDRϪ/Ϫ mice, both by whole-body Ca determination and histomorphometric evaluation; the number of osteoclastic cells in bone was increased. The fetuses were hypercalcemic and had a 5-fold increase in circulating 1,25(OH) 2 D 3 . We then studied pregnancies in VDRϪ/Ϫ females, mated with wt males, fed a high Ca/P/lactose rescue diet during pregnancy. The rescue diet normalized the mineralization, the number of osteoclastic cells, and plasma Ca and 1,25(OH) 2 D 3 concentrations in the fetuses. We interpret the data as evidence that, to ensure normal fetal mineralization, the maternal VDR-dependent intestinal Ca absorption can be substituted by passive Ca absorption entrained by a higher Ca intake. Several strains of mice with a disrupted VDR gene have been generated, including the Tokyo-strain (7), the Bostonstrain (8) and the Leuven-strain (9). VDR-null mice show rickets and osteomalacia, with abnormal Ca homeostasis in-