Neurotrophins regulate neuronal survival and phenotypic differentiation. Recent evidence also suggests a role in the modulation of synaptic activity. Using neuronal cell cultures from embryonic hippocampus, we previously found that application of brain-derived neurotrophic factor rapidly enhanced synaptic transmission. We now report that application of neurotrophin-4, another ligand for the trkB neurotrophin receptor, was equally effective in enhancing synaptic currents. In contrast, nerve growth factor, neurotrophin-3, basic fibroblast growth factor and epidermal growth factor did not share this action. Our results suggest that activation of trkB receptors plays a selective role in the regulation of synaptic efficacy in the hippocampus.