SummaryCystinotic fibroblasts contain highly elevated amounts of intraellular non-protein cystine within lysosomes compared to normal fibroblasts. Both the rate of cystine reaccumulation by cystin-delepleted cystinotic fibroblasts and the steady-state cystine content of nondepleted cystinotic fibroblasts can be modulated by the addition of bovine scrum albumin to the culture medium. This effect is not seen in cultures of normal and cystinotic heterozygote fibroblasts. The cystinotic homozygote cells accumulate cystine under these conditions from proteolysis of the albumin. An increased rate of pinocytosis or proteolysis of albumin does not account for the observed cystine accumulation by the cystinotic fibroblasts. Comparison of the amount of cystine accumulated to the amount of albumin degraded shows that less than one percent of the cystine moieties released by proteolysis is retained within these cells.SpeculationThe metabolic defect leading to cystine storage in cystinosis remains to be identified. Study of the relationship between the rate of cystine accumulation and the cystine and cysteine content of proteins degraded by cystinotic fibroblasts may help to determine if the defect is related to an abnormality of lysosomal disulfide reduction.