Historical background regarding cross-correction of lysosomal enzyme deficiencies in cultured cells. Small amounts of high-uptake lysosomal enzymes secreted by normal fibroblasts (thin arrows) were found to be taken up by fibroblasts from a patient with a genetic lack of a single lysosomal enzyme, correcting that deficiency. In contrast, I-cell disease fibroblasts secrete large amounts of multiple lysosomal enzymes of the low-uptake variety (thick arrows). The latter forms cannot correct lysosomal enzyme deficiencies in other cells. However, I-cells retain the capability to accept high-uptake enzymes secreted by other cells (thin arrows). Uptake was blocked by the addition of mannose 6-phosphate (M6P) to the media.