Extracellular ATP induced changes in the membrane potential of thymocytes from BALB/c mice were analyzed. At concentrations below 0.1 mM, ATP hyperpolarizes the cell membrane on the time scale of development of the Ca(2+)-signal. After a longer time hyperpolarization turns to depolarization. ATP concentrations higher than 0.5 mM caused rapid depolarization without previous hyperpolarization. Verapamil, quinine or the absence of extracellular Ca2+ blocked the hyperpolarization by ATP. In Na(+)-free medium the magnitude of depolarization decreased. Our data suggest a contribution of Ca(2+)-activated K+ channels to the hyperpolarizing effect of ATP at lower concentrations. The direction of membrane potential changes is determined presumably by a sensitive balance of ATP-receptor mediated Ca(2+)- and Na(+)-influx and the Ca(2+)-activated K(+)-channel activity.