Calcium oxalate stone formation was induced in rats by oral application of ethylene glycol and ammonium chloride for 4, 8 and 24 days. After each induction period, light-microscopically, birefringent crystals were seen in the tubular lumen and, intracellularly, in proximal and distal tubular cells. After a postfixation which partially removed the crystalline material crystal ghosts were seen by electron microscopy. In the lumen, crystal ghosts were observed ranging from single crystals to crystal agglomerates. The large intraluminal agglomerates were surrounded by epithelial cells and cellular debris. Both crystal types had an organic interior. In the cytoplasm of ultrastructurally changed proximal tubular cells, small (200 to 600 nm. in diameter) single crystal ghosts were present in the terminal web at the basis of the microvilli. Others were present in large vacuolar structures, with a fine granular matrix. After the prolonged microlith induction periods, such vacuolar structures were seen throughout the cell. The organic matrix of the crystal ghosts therein had acquired a more aggregated and complex structure.