Brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission among the hippocampal neurons in the resting state. This mechanism may be due to the phosphorylation of NMDA receptors through its Trkb receptors on the postsynaptic neuron. In contrast, BDNF also has a suppressing effect on the synaptic transmission via non-NMDA receptors. The activities of non-NMDA receptors are known to modulate the NMDA receptors activities. This study was to investigate, using patch clamp technique, whether the BDNF increases or decreases the glutamate-induced synaptic transmission in which glutamate acts on both NMDA- and non-NMDA receptors. When a postsynaptic neuron was previously excited by a large amount of glutamate, BDNF decreased the synaptic transmission induced by subsequently-applied glutamate. However, when the signal entered into a postsynaptic neuron was blocked by the application of tetrodotoxin, BDNF increased the glutamate-induced responses. These results show that BDNF plays a role in a protection of the neurons against hazardous or uncontrolled activation of glutamate receptors and in an accentuation of the synaptic response when the signal is inevitably diminished.