The cartilage of epiphysis and cuboid bones from three Beagle puppies bred from parents with a constant heredity of multiple epiphyseal dysplasia, was examined macroscopically, histomorphologically and histochemically. The puppies were euthanized at the age of one week, three weeks and five weeks, respectively. The investigation showed the foci of the disease develop in a broad subarticular zone where normally strong three-dimensional growth of the cartilage takes place. The first signs of the disease appeared about the time of birth and new foci reached a climax when the puppies were about three weeks old. Histomorphological and histochemical examination of the cartilage showed that the disease developed in a sequence of confluent stages. In the initial stage, there was an accumulation of abnormal cartilage matrix in the chondrocyte and/or chondrocyte lacunae. The abnormal substance consisted apparently of concentrated or free chondroitin sulphates not bound to protein. Then followed a second stage of liquefaction and coalescence of the abnormal cartilage matrix which formed cysts of different sizes, some of them visible macroscopically. In the third stage of calcification of the cyst content and surrounding abnormal cartilage, it was found that the calcium was deposited in grains bound to chondroitin sulphates. The results of the present study of the pre-calcification stage of the disease in Beagle dogs seem to be comparable with or equivalent to the results of the study of the post-natal stage of the disease in children and may explain something of the prenatal pathogenesis in children.