We are investigating the complex proteoglycans of connective tissue with respect to their structures, their aggregating tendencies, and their interactions with model compounds. Methods are being developed to improve the efficiency of separation of the non-covalently bound ligands, and also to determine the range of composition of the covalently bound macromolecules and to piece together the structural features by a study of the degradation products. The latter includes developing methods of separation of the single chain polysaccharides from the multichain intermediates and from the poly chain intact macromolecules. The difference in chain length of the single chains and their variations in different tissues and sources are also under investigation. With the accrued experience in handling these complex macromolecules we are studying transplantable mouse chondrosarcomas and related human pathological connective tissues.