Factors underlying paired-pulse facilitation (PPF) were studied by intracellular and field recordings of CA1 neurons in the hippocampal slice in vitro, following stimulation of the Schaffer collaterals apical dendritic afferents. Similar magnitudes of PPF were found using the slopes or peaks of the excitatory postsynaptic potentials (EPSPs) recorded intracellularly or extracellularly at the soma or dendrites. The paired-pulse EPSP facilitation index (EPI), defined as the ratio of EPSP slope evoked by the second pulse (E2) to that evoked by the first pulse (E1), had a broad peak at 30-60 ms interpulse interval (IPI). EPI was largest at small E1 and decreased with an E1 increase. Spiking excitability was enhanced after the second as compared to the first pulse as evidenced by (1) a decreased latency to fire and (2) an increased tendency to fire double or multiple spikes. The PPF of spiking resulted partly from an increased E2 and partly from a diminished inhibition evoked by the second pulse. Whether the first pulse elicited a spike or not had no significant effect on the EPI. Multiple spiking evoked by the second pulse was partly blocked by the GABAB antagonist CGP35348 (1 mM). The PPF of the EPSP slopes, however, was not significantly affected by GABAB antagonists, GABAA antagonist bicuculline or NMDA antagonist 2-aminophosphonovalerate. In conclusion, PPF may serve as a means of amplification of synaptic transmission such that reliable spike output may result from a given set of synapses.