A slow prepotential preceding the action potential elicited by 40-80 ms depolarizing current pulses injected in CA1 pyramidal cells in rat hippocampal slices was isolated and characterized using a subtraction procedure. The exponentially rising slow prepotential showed enhanced amplitude at depolarized membrane potential levels. In sufficient doses, intracellular injection of the lidocaine derivative QX-314 selectively blocked the slow prepotential, leaving the action potential largely unchanged. These results suggest that the slow prepotential might be mediated by a persistent sodium conductance or threshold channels recently found in various nerve cells, and could trigger action potentials in situations with a long-lasting depolarization.