The sensitivity to GABA of Purkinje cells in thin cerebellar slices was examined by recording either spontaneous inhibitory synaptic currents or ionic currents elicited by local GABA applications. The effects of Ca2+ entry induced by depolarizing voltage pulses were opposite for the two types of currents. Currents due to exogenous GABA applications were increased by a train of voltage pulses. This potentiation was transient with an average half recovery period of 3.7 min. Spontaneous synaptic currents were reduced by depolarizing voltage pulses, with a half recovery time of about 20 s. The inhibition was largely explained by a decrease of the frequency of synaptic events, suggesting that the primary location of the effect was presynaptic. Thus, a Ca2+ rise increases the sensitivity of Purkinje cells to GABA and induces a retrograde inhibition of presynaptic terminals. The latter effect may be due to a diffusible Ca2(+)-dependent messenger.