1. Vitamin D-deficient chicks, maintained on a diet adequate in calcium and treated with ethane-1-hydroxy-1,1-diphosphonate for 2 days before a single oral dose of cholecalciferol (vitamin D3), converted the vitamin into 24,25-dihydroxycholecalciferol instead of into the normal metabolite 1,25-dihydroxycholecalciferol.
2. This inhibition of the renal 1-hydroxylase disappeared on withdrawal of the diphosphonate.
3. Kidneys from chicks given diphosphonate for 12 days converted 25-hydroxycholecalciferol into 24,25-dihydroxycholecalciferol on incubation in vitro.
4. The inhibition of the 1-hydroxylase was markedly accelerated by treating the birds with cholecalciferol.
5. No inhibition of renal 1-hydroxylation was observed in birds maintained on a diet low in calcium.
6. A possible mechanism producing this effect is discussed.