Voltage-activated high- and low-threshold Ca2+ currents were studied using whole-cell voltage-clamp techniques and fura-2 fluorescence measurements of intracellular Ca2+ in neurons acutely isolated from rat neostriatum. High-threshold Ca2+ currents activated around -40 mV and were present in at least 95% of neostriatal neurons. The maximum current, 736 +/- 44 pA (mean +/- SEM, n = 141), was observed around 0 mV. In 70% of neurons, high-threshold Ca2+ currents exhibited both inactivating and noninactivating components. The majority of the high- threshold Ca2+ currents appeared to belong neither to the “L-type” nor the “N-type” classification, since omega-conotoxin (5 microM) decreased this current by only 29% and nimodipine (10 microM) decreased the noninactivating component of this current by only 17%. A low-threshold transient (T-type) Ca2+ current was observed in 40% of neurons. When both T-type and high-threshold Ca2+ currents were present, their maximum amplitudes were 78 +/- 7 pA and 800 +/- 57 pA, respectively (mean +/- SEM, n = 58). At a holding potential of -100 mV, the T-type Ca2+ current activated around -60 mV, with maximum current near -40 mV. Steady-state inactivation of the T-type Ca2+ current was observed at holding potentials positive to -125 mV, and the current was half- inactivated at -88 mV. Recovery from inactivation to 90% of maximum occurred within 800 msec. Mn2+ or Co2+ (3 mM) blocked both high- threshold and T-type Ca2+ currents, whereas Cd2+ (25 microM) or verapamil (50 microM and 150 microM) preferentially blocked high- threshold over T-type Ca2+ currents. In response to depolarization by 50 mM K+, fura-2 fluorescence measurements showed increased intracellular Ca2+ in both the soma and the proximal dendrites of neostriatal neurons that was markedly reduced by 25 microM Cd2+. These findings suggest that high-threshold Ca channels are present in both the soma and proximal dendrites of neostriatal neurons.