Two lysosomal enzymes have been selected for intensive study: alpha-L-iduronidase, the enzyme deficient in the Hurler syndrome, and sulfoiduronate sulfatase, the enzyme deficient in the Hunter syndrome. The project focuses on improved methods of purification and assay in order to: 1) improve diagnostic procedures; 2) prepare antibodies to determine the presence or absence of cross reactive proteins in fibroblasts of patients; 3) determine the chemical differences between isozymes that enter fibroblasts (and function as "corrective factors") and those that do not; 4) determine the difference between the normal isozymes and their counterpart produced by patients with mucolipidoses; and 5) prepare enough purified enzyme for a clinical trial of enzyme replacement.