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Summary1. A theory has been proposed by Neuman that some metabolites which contain phosphate groups can act in the body as crystal poisons and so influence the deposition of calcium salts in skeletal structures. This theory is explained and the evidence for it reviewed.2. A crystal poison is a compound which settles on the surface of a crystal and interferes with the continued formation of the crystal lattice. Thus crystal growth stops and the mother liquor may become supersaturated.3. The evidence in favour of the theory is considered, both for phosphatic skeletons such as bone and calcareous skeletons such as those found in many invertebrates.4. Many of the phosphate groups in metabolites can produce the inhibitory effect and it has been suggested that a phosphatase enzyme acts in destroying these crystal poisons by hydrolysing them at the site of mineralization.5. Pyrophosphates are effective crystal poisons at very great dilutions, and yet they have been shown to be present in ossifying bones and in the plasma and urine of mammals.6. Alkaline phosphatase is present during the formation of calcareous skeletons, but the explanation of the removal of a crystal poison by hydrolysis is complicated by the fact that orthophosphates also inhibit calcification.7. These data are discussed in relation to the physiology of calcification in animals with phosphatic and with calcareous skeletons and some of the implications of the theory are evaluated.

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