Hippocampal long-term potentiation (LTP) is a remarkably stable facilitation of synaptic responses resulting from very brief trains of high-frequency stimulation. Because of its persistence and modest induction conditions, LTP represents a promising candidate for a substrate of memory. Some progress has been made in localizing the changes responsible for the effect; for example, it has been shown that LTP is not accompanied by changes in the fibre volleys of the test afferents or by generalized alterations of the dendrites of their target cells. However, it is unknown whether the potentiation is due to pre- or postsynaptic changes and there is evidence in favour of each (for example, see refs 5, 6). We now report that intracellular injections of the calcium chelator EGTA block the development of LTP. These results strongly suggest that LTP is caused by a modification of the postsynaptic neurone and that its induction depends on the level of free calcium.