An electron microscopic investigation of the relationship between proteoglycans and cartilage mineralization has been carried out. On the basis of the number of matrix granules and the affinity of the matrix for colloidal ThO 2, we found that in embryonic mouse radii: 1. 1. The amount of proteoglycans does not decline before the onset of mineralization. 2. 2. In the calcified portions of the cartilage matrix the concentration of proteoglycans remains constant during and after mineralization. 3. 3. There is a degradation of proteoglycans in the uncalcified portions of the matrix near the marrow cavity. This last finding explains why chemical analyses of epiphyseal disks so often show a decline in the amount of proteoglycans in the mineralizing zones. It was concluded that degradation of proteoglycans is not a first, necessary step in cartilage mineralization. The loss of proteoglycans in the uncalcified matrix in the lower zones of the epiphyseal disks is probably devoid of any particular significance for calcification but is rather a preparation for the formation of the marrow cavity.