Thallium sulfate induced achondroplasia has been studied in the embryonic chick by culturing the tibiae from normal embryos in embryo extract from thallium sulfate treated embryos; by injecting normal embryos with homogenates of thallium sulfate treated embryos; and by the coinjection of thallium sulfate and cortisone acetate or vitamin C, and analysis of the tibiae for growth, histology, histochemistry (collagen, acid mucopolysaccharide, glycogen, calcium, alkaline phosphatase), hexosamine, and hydroxyproline activity.Tibiae from untreated embryos organ cultured in embryo extract from thallium sulfate treated embryos, and tibiae of host embryos injected with homogenates from thallium sulfate treated embryos, exhibited normal growth, histology, histochemistry, hydroxyproline, and hexosamine activity. Thus the achondroplasia observed in thallium sulfate treated embryos does not result from the production of an inhibitor to normal chondrocyte growth and function which is transmissible in saline extracts. This is in contrast to some genetic achondroplasias.Coinjection of thallium and vitamin C or of thallium and cortisone acetate (agents increasing or decreasing collagen and hexosamme-containing acid mucopolysaccharide synthesis respectively) resulted in potentiation of the syndrome in the presence of cortisone acetate, and alleviation of the syndrome in the presence of vitamin C. Vitamin C prevented the production of the defective cartilage matrix characteristic of the long bones of embryos treated with thallium sulfate alone.It was concluded that abnormalities in acid mucopolysaccharide and collagen release from chondrocytes and deposition in the cartilaginous matrix were possible causes of the chondrocyte necrosis, achondroplasia, and micromelia characteristic of the achondroplastic syndrome.