The effect of increased impulse activity upon voltage-dependent Ca2+ currents was studied in the cell body of a crayfish phasic motoneuron using two-electrode voltage-clamp technique. Increased electrical activity in this relatively inactive motoneuron produces a short-term and long-term reduction in the voltage-dependent Ca2+ current. Both forms of activity-dependent reduction in Ca2+ current are Ca2+ dependent. The short-term reduction in Ca2+ current appears to involve the Ca(2+)-dependent inactivation of Ca2+ channels, previously described in a variety of neurons. The long-term reduction in Ca2+ current is produced by prolonged Ca2+ influx and persists for days: in vivo stimulation of the phasic motor axon at 5 Hz for 1 hr results in a 30% reduction in Ca2+ current density, which persists for at least 3 d. Both the short-term and long-term reductions in Ca2+ current appear to result from changes in a single type of high-voltage-activated (HVA) Ca2+ channel. Inhibition of protein synthesis attenuates the long-term reduction in Ca2+ current and has no effect upon the short-term Ca2+ current reduction. During the long-term reduction in Ca2+ current, it appears that Ca2+ channels located distant to the site of Ca2+ influx are affected. The relationship of these results to a previously described Ca(2+)-dependent reduction in transmitter release is discussed.