The complex pleiotropic pattern of damage caused in chick embryos by the talpid3 gene has been described previously by Ede & Kelly (1964a, b) and Hinchliffe & Ede (1967). The pattern of segregation of the mesenchyme in forming the precartilaginous or membranous skeleton is abnormal, and the resulting cartilaginous skeleton shows characteristic fusions of the vertebrae and of the limb elements. By 11 days of development there is a complete failure of cartilage-replacement bone to appear, even in the more normally formed cartilage rudiments (e.g. ribs, scapula, coracoid, ilium). By contrast, ossification to give the membrane bones (the clavicle and bones of the skull and jaws), which are formed directly from condensations in the mesenchyme, proceeds normally. This paper describes the attempts made by experimental and histochemical means to account for the failure of cartilage-replacement bone formation.