Children with nephropathic cystinosis store 50 to 100 times normal amounts of free cystine in many cells and display negligible lysosomal cystine transport in their leucocytes and cultured fibroblasts. A patient with intermediate (adolescent) cystinosis exhibited a similar deficiency of egress out of fibroblast lysosome-rich granular fractions. Another individual with benign (adult) cystinosis accumulated only 2.85 nmol 1/2 cystine/mg leucocyte protein, or 20-50% of the amount stored in nephropathic cystinosis leucocytes. His leucocyte granular fractions also displayed substantial residual cystine-carrying capacity, as determined by measurement of lysosomal cystine countertransport. We conclude that the variant forms of cystinosis represent a continuum of lysosomal cystine storage, with the varied clinical presentation depending on the amount of residual cystine-carrying capacity, genetic predispositions, and differential tissue susceptibilities.