Abstract1. Various phosphonates, which are compounds containing C‐P bonds, have been studied to see whether they are able to inhibit, in a manner similar to that of pyrophosphate and the condensed phosphates, the crystallization of calcium phosphatein vitroand the pathological calcification of the aorta and the kidneys of rats given large amounts of vitamin D3.2. Six of the ten compounds studied markedly increased the minimum product, [Ca] × [P], required to induce the precipitation of calcium phosphatein vitrounder physiological conditions of pH, ionic strength and temperature. Inhibition was observed at concentrations as low as 10‐7—106M.3. Most of the diphosphonates, particularly those possessing P‐C‐P bonds, showed some ability to inhibit the calcification of the aortas and kidneys of rats treated with large amounts of vitamin D3. The most effective inhibitors were methylene diphosphonate (MDP), ethane‐1‐hydroxy‐1: I‐diphosphonate (EHDP) and diehloromethylene diphosphonate (Cl2MDP).4. The phosphonates that possess P‐C‐P bonds thus appear to have effects on the deposition of calcium phosphatein vitroandin vivosimilar to those of inorganic pyrophosphate and the condensed phosphates, which possess P‐O‐P bonds. These phosphonates differ from the condensed phosphates in that they inhibit kidney calcification as well as aortic calcification and are active by mouth as well as parenterally. The wider spectrum of activity of the phosphonatesin vivomay be due to the fact that they are more resistant to chemical and enzymic breakdown.5. Phosphonates might be used therapeutically in man against diseases in which calcium sal