The generation of long-term potentiation of synaptic transmission in area CA1 of hippocampal slices of the guinea-pig has been examined in solutions containing low concentrations of magnesium ions. It was found that the induction of long-term potentiation is greatly facilitated in slices perfused with 0.1 mM magnesium but much less so with 0.5 mM magnesium solution. The long-term potentiation evoked by brief tetanization in 0.1 mM magnesium was prevented following application of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate. Moreover, the response to tetanization, recorded in the dendritic layer, contained a much greater than normal component blocked by 2-amino-5-phosphonovalerate. The latter represents current through postsynaptic N-methyl-D-aspartate receptor channels, suggesting that the facilitation of long-term potentiation is related to a facilitated opening of these channels. The results support the notion that the generation of long-term potentiation is related to current through N-methyl-D-aspartate receptor channels which is under the control of extracellular magnesium ions.