The neurotrophins are a family of neurotrophic factors that promote survival and differentiation of various neuronal populations. Although the long-term effects of neurotrophins on neuronal survival and differentiation have been intensively studied, nothing is known about their effects on synaptic function. Here we report that acute exposure to neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF), but not nerve growth factor (NGF), rapidly potentiates the spontaneous and impulse-evoked synaptic activity of developing neuromuscular synapses in culture. The effect appears to be presynaptic in origin and to be mediated by the Trk family of receptor tyrosine kinases. These results provide evidence for the regulation of the function of developing synapses by neurotrophins.