The effect of different concentrations of LiCl or KCl (0.6-20 meq/liter) on PHA-stimulated lymphocytes from young, old, and Down's syndrome subjects was studied. LiCl showed a dramatic enhancing effect on [3H]thymidine incorporation induced by a suboptimal dose of PHA in old subjects and Down's syndrome patients. An increase of [3H]thymidine incorporation in human lymphocytes stimulated by a suboptimal dose of PHA was also observed with KCl. This effect was higher in old subjects than that observed in young and Down's subjects. LiCl and KCl can modulate and partially restore the derangement in early events of mitogen stimulation which seems to be present in lymphocytes from both old and Down's syndrome subjects.