A combination of clinical, genetic, morphologic and biochemical approaches has permitted firm delineation of several distinct mucopolysaccharidoses. Recent additions to the morphologic methods for studying these conditions include demonstration of metachromasia in fibroblasts and monocytes and electronmicro-scopic identification of swollen lysosomes. Cross correction of metabolic and morphologic abnormalities in fibroblasts when mixed is evidence of nosologic distinctness of entities. It is remarkable how accurately one can recognize on clinical grounds alone six entities listed in Table I once they have been distinguished by the supplementary methods; at least recognition by about age eight is usually easy. This does not mean that atypical cases which probably represent new entities are not, in the aggregate, rather frequent. Advance of knowledge in a field tends to cloud it for a time and an area which had seemed very simple becomes temporarily confused, and then again becomes simple when the knowledge advances even further. The mucopolysaccharidoses are in a confused state presently which we can expect to be rectified in the next few years. © 1969.