LaCl3 stimulated the initial rate of 45Ca2+ exchange measured under steady-state conditions in isolated liver cells. Cu2+ greater than La3+ = Fe3+ greater than Fe2+ = Zn2+ greater Ni2+ greater than Mn2+ also stimulated 45Ca2+ exchange. Compartmental analysis of 45Ca2+-exchange curves obtained in the presence or absence of La3+, and in the presence or absence of adrenaline, showed that the predominant effect of La3+ is to stimulate the inflow of Ca2+ to the cell from the medium. No evidence for an inhibition of Ca2+ outflow from the cell was obtained. In the presence of La3+, adrenaline caused no further stimulation of Ca2+ inflow to the cell. In the absence of adrenaline, La3+ increased the uptake of Ca2+ (measured by atomic-absorption spectroscopy) by isolated hepatocytes incubated at 1 degree C. The proposal that La3+ stimulates Ca2+ inflow to the liver cell by inducing a conformational change in the Ca2+-inflow transporter of the plasma membrane is briefly discussed.