Purpose: The present studies assessed the possibility that high concentrations of oxalate may be toxic to renal epithelial cells. Materials and Methods: Subconfluent cultures of LLC-PK1 cells were exposed to oxalate, and the effects on cell morphology, membrane permeability to vital dyes, DNA integrity and cell density were assessed. Results: Oxalate exposure produced time- and concentration-dependent changes in the light microscopic appearance of LLC-PK1 cells with higher concentrations (> 140 mu M.) inducing marked cytosolic vacuolization and nuclear pyknosis. Exposure to oxalate also increased membrane permeability to vital dyes, promoted DNA fragmentation and, at high concentrations (350 mu M. free oxalate), induced a net loss of LLC-PK1 cells. Conclusions: Since high concentrations of oxalate can be toxic to renal epithelial cells, hyperoxaluria may contribute to several forms of renal disease including both calcium oxalate stone disease and end-stage renal disease.