AbstractCalciphylaxis is a local tissue calcific reaction at the site of an injection of challenger substance given a critical time period after the oral administration of a sensitizer substance such as dihydrotachysterol (DHT), vitamin D or parathormone. Cutaneous calciphylaxis is readily induced in the rat but not in the mouse and this may be because, in the latter, the challenger substance is absorbed rapidly by macrophages. In the rat the administration of 500 ug/0.1 ml of DHT followed after 24 h by the subcutaneous (SC) injection of ferric chloride (FeCl3) (30 ug/0.1 ml) is followed rapidly by calcification of the SC site. There is an early transient acute inflammatory reaction with the incrustation of collagen fibres by the iron salt and an apparent exudation of calcium and phosphate ions from the bloodstream. These ions also become associated with collagen fibres. Two days after injection macrophages and multinucleated giant cells become the dominant cells. Calciphylaxis is a useful experimental model of ectopic calcification and is associated with an initial hypercalcaemia. The diphosphonates ethane‐l‐hydroxy‐1, 1‐diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) are effective inhibitors of the calciphylactic reaction when administered prior to the initiation of the experimental pr