The whole-cell patch-clamp technique was used to record Ca2+ currents in acutely dissociated neurons from layer II of guinea-pig piriform cortex (PC). Ba2+ (5 mM) was used as charge carrier. In a subpopulation of layer II cells ( approximately 22%) total Ba2+ currents (IBas) displayed a high degree (> 70%) of inactivation after 300 ms of steady depolarization. The application of L-, N- and P/Q-type Ca2+-channel blockers to these high-decay IBas left their fast inactivating component largely unaffected. The inactivation phase of the blocker-resistant, fast-decaying IBa thus isolated had a bi-exponential time course, with a fast time constant of approximately 20 ms and a slower time constant of approximately 100 ms at voltage levels positive to -10 mV. The voltage dependence of activation of the blocker-resistant, fast-decaying IBa was shifted by approximately 7-9 mV in the negative direction in comparison with those of other pharmacologically and/or kinetically different high-voltage-activated Ca2+ currents. We named this blocker-resistant, fast-decaying, intermediate-threshold current IRfi. The amplitude of IRfi decreased only slightly (by approximately 9%) when extracellular Ca2+ was substituted for Ba2+, in contrast with that of slowly decaying, high-voltage-activated currents, which was reduced by approximately 41% on average. Moreover, IRfi was substantially inhibited by low concentrations of Ni2+ (50 microM). We conclude that IRfi, because of its fast inactivation kinetics, intermediate threshold of activation and resistance to organic blockers, represents a definite, identifiable Ca2+ current different from classical high-voltage-activated currents and clearly distinguishable from classical IT. The striking similarity found between IRfi and Ca2+ currents resulting from heterologous expression of alpha1E-type channel subunits is discussed.