Depolarizing effects of increasing concentrations of extracellular K(+), as well as the repolarizing effect of bretylium tosylate (BT) were evaluated in human lymphocytes from young and elderly volunteers. Cells from elderly volunteers were less responsive to depolarization induced by increased extracellular potassium concentrations than those from young volunteers. Upon a near complete depolarization induced by 140 mM K(+) in the extracellular space, a significant amount of non-responding cells were found in samples from elderly volunteers. BT, which opens the otherwise silent Na(+) channels of partially depolarized cells, with subsequent activation of the Na(+)-K(+) pump (Pieri et al., 1989). repolarized both young and old lymphocytes. However, the degree of the repolarization was only 40% in the case of lymphocytes from elderly volunteers than from that of the young. It is suggested that an increase of membrane microviscosity, characteristic of old cells, may be at least partially responsible for the decreased responsiveness of plasma membrane functions which were observed.