In vitro stimulation of two axonal branches from hippocampal CA3 pyramids, the CA1 afferent Schaffer collaterals and the CA3 efferents to septum through fimbria, released D-[3H]aspartate as a measure for endogenous L-glutamate. Following bursts of repetitive electrical stimuli to the Schaffer collaterals, a long-lasting and significantly increased resting efflux, as well as an increased stimulus evoked release of D-aspartate, appeared. No such persistent increase in D-aspartate efflux was recorded from the septal terminals. We propose that increased transmitter liberation may account for long-term synaptic potentiation in hippocampus.