The effects of the N-methyl-D-aspartate receptor antagonists 2-amino-5-phosphonovalerate and gamma-D-glutamylglycine on the induction of long-lasting potentiation in the CAl and dentate areas of the hippocampal slice preparation have been examined. Synaptic activity was recorded extracellularly in the dendritic layer as a field excitatory postsynaptic potential, and the amount of long-lasting potentiation produced was measured from the change in slope of the rising phase of this potential. Experiments were generally performed with the gamma-aminobutyric acid antagonist picrotoxin in the solution. It is shown that 2-amino-5-phosphonovalerate prevents the induction of long-lasting potentiation following afferent tetanization of an input, without any effect on other inputs projecting to the same postsynaptic neurons. This result makes it unlikely that the preventive action of 2-amino-5-phosphonovalerate is related to any unspecific depressive action. Instead, 2-amino-5-phosphonovalerate was observed to block a postsynaptic depolarizing process appearing during the tetanus, likely related to current through synaptically activated N-methyl-D-aspartate receptor channels. It is suggested that 2-amino-5-phosphonovalerate prevents the induction of long-lasting potentiation by blockade of these currents through its antagonistic action on the N-methyl-D-aspartate receptors. Application of gamma-D-glutamylglycine similarly prevented the induction of long-lasting potentiation. No potentiation appeared following wash-out of the drug. The results exclude the possibility that the preventive action of this drug is related to a mere masking action on long-lasting potentiation induced in presynaptic terminals. It is suggested that gamma-D-glutamylglycine blocks the induction of long-lasting potentiation by its antagonistic action on the N-methyl-D-aspartate receptors, i.e. in a manner similar to that of 2-amino-5-phosphonovalerate.