The possibility of enzyme replacement in lysosomal storage diseases requires extensive knowledge of the physiology and biochemistry of cells and their organelles, especially, the lysosome in the condition of storage. Animals treated with drugs (suramin, chloroquine) simulated lysosomal storage disease. Study of physiologic and biochemical aberrations in treated animals will define the milieu in which enzyme replacement can be attempted. Of particular interest is the ability of treated animals to incorporate infused enzymes, the function of receptors on plasma and lysosomal membranes, the ability of incorporated enzymes to interact with storage material, and the targeting of enzyme to cells and prolongation of their biologic activity in situ. Physiologic alterations are appropriately studied in animals, whereas, more detailed biochemical studies are more suitably conducted in strictly defined cell suspensions and cell cultures. Studies employing animal cells including macrophages, fibroblasts, hepatocytes, and Kupffer ceells will be performed. Also, cultures of human fibroblasts and peripheral macrophages from control and disease states will be utilized.