Background. Cystinosis is an autosomal recessive disorder characterized by excessive accumulation of cystine in the lysosomes of the cell. The disease is caused by a defective cystine transporter, cystinosin, in the lysosomal membrane which mediates cystine efflux from the lysosome to the cytosol (1). Cystinosis affects almost all cells and tissues but the kidney involvement remains the foremost clinical characteristic of the disorder which is manifested clinically by a generalized dysfunction of proximal tubular transport of glucose, amino acids, phosphate and essential ions resulting to Fanconi’s syndrome (2). Initial investigations on the pathogenesis of cystinosis were hampered by inability to achieve elevated intracellular concentrations of cystine. This hurdle was eventually solved when it was demonstrated that the methyl ester derivative of cystine leads to the accumulation of cystine in the lysosomes in vitro and in vivo (3,4). Aim. In this study, we investigated the effect of cystine dimethyl ester (CDME) on the viability of LLC-PK₁ cells, an epithelial cell line originally derived from porcine kidneys and expresses many functions and characteristics of the proximal tubular cells. Methods. A colorimetric assay based on the reduction of tetrazolium salt WST-1 into a colored formazan dye by succinate-tetrazolium reductase in viable cells was used as a measure of the net metabolic activity of cells following incubations at different concentrations of CDME (0.1 to 1 mM). Results. Incubation of LLC-PK₁ cells with low CDME concentrations (0.1 and 0.2mM) for 60 and 120 minutes resulted in an increase in WST-1 absorbance associated with enhanced mitochondrial metabolism, which may be related to higher demand for ATP (139% of control at 0.1 mM CDME for 60 minutes to 372% of control at 0.2 mM CDME for 120 minutes, p<0.05). However, the viability of the cells subsequently dropped to less than 15% of control (p<0.05) upon incubation with higher concentration of CDME (1mM) for 30, 60 and 120 minutes, indicating the acute lethal effect of CDME at high concentration. It can be speculated that exposure of non-cystinotic cells to high levels of CDME alters the metabolism and redox status of the cells sufficiently to trigger cell death.