Although the effects of neurotrophins on survival and differentiation of various neuronal populations have been well studied, little is known about their role in synaptic development and function. We have investigated the long-term effects of neurotrophins in the maturation of neuromuscular synapses in Xenopus nerve-muscle cocultures. BDNF and NT-3, but not NGF, elicited significant changes in several properties of spontaneous synaptic currents (SSCs), indicative of more mature synapses. Most synapses treated by the neurotrophins exhibited a bell-shaped distribution of SSC amplitudes, which reflects mature quantal secretion. The neurotrophins also potentiated the efficacy and reliability of stimulus-induced synaptic transmission. Moreover, BDNF and NT-3 increased the levels of the synaptic vesicle proteins, synaptophysin, and synapsin 1 in the spinal neurons. The number of varicosities per neuron also showed a significant increase after neurotrophin treatment. The effects of the neurotrophins appear to be mediated by the Trk family of receptor tyrosine kinases, primarily through a presynaptic mechanism. These results suggest that BDNF and NT-3 promote functional maturation of synapses.