Cell culture of skin fibroblasts seems to offer a means by which inherited disorders of mucopolysaccharide metabolism may be investigated. Since skin fibroblasts are readily available by biopsy and grow well in culture, a cell involved in the metabolic defect can be examined under controlled conditions. Cellular metachromasia, as evidenced by red cytoplasm on staining with toluidine-blue O, seems to be a reliable genetic marker for investigating mucopolysaccharidoses. The Morquio syndrome, in which the abnormalities are restricted to the skeletal system, seems to be an exception, and this suggests that the abnormal gene is suppressed in skin fibroblasts in this condition. Although these studies have been concerned primarily with the inherited disorders of mucopolysaccharide metabolism, the methodology appears applicable to other genetic disorders, associated with an intracellular accumulation of a normal or abnormal metabolic product.