The toxic effect of ammonium upon a variety of cell lines of lymphoid (Jurkat), pituitary (GH(4)), and renal (LLC-PK1) origin was studied. Millimolar concentrations of the ion mildly affected the growth of GH(4) cells and prevented the growth of LLC-PK1 cells. The ion did not lead to the death of LLC-PK1 cells but it produced morphologic changes in these cells. The effects of ammonium upon Jurkat cells were different because cells died after accumulating at S phase. Cell death was due to apoptosis and might be related to ammonium-induced calcium mobilization from intracellular stores. These results indicate that the toxic effects caused by ammonium accumulation are different depending upon the cell type.