In primary cultures of hippocampal neurons, activation of GABAB receptors reversibly inhibits high-voltage activated (HVA) Ca currents. In some neurons the GABAB agonist baclofen produces slow down of Ca current activation. In these cells the inhibitory action of the agonist can be relieved by strong pre-conditioning depolarizations. In other cells, where no significant changes in activation kinetics could be observed during agonist application, conditioning prepulses are nearly ineffective to recover the current from inhibition. Thus, in hippocampal neurons, activation of GABAergic receptors can modulate Ca currents with two different modes: one is voltage-dependent and the other is voltage-independent. In the presence of omega-conotoxin (omega-CgTx), only the second mode is prevented, suggesting that the two modulatory mechanisms (voltage-dependent and voltage-independent) operate in different cells on separate classes of HVA Ca channels.