Long-term potentiation (LTP), the increase in synaptic strength evoked by high-frequency stimulation, is often considered to be a cellular model for learning and memory. The validity of this model depends on the assumptions that physiological stimuli can induce LTP in vivo and that the resulting synaptic modifications correlate with behavioural changes. However, modifiable synapses are generally embedded deep in complex circuits. In contrast, the goldfish Mauthner (M)-cell and its afferent synapses are easily accessible for electrophysiological studies, and firing of this neuron is sufficient to trigger fast escape behaviour in response to sudden stimuli. We have previously shown that tetanic stimulation can induce LTP of the feedforward inhibitory synapses that control the excitability of the M-cell. Here we report that natural sensory stimulation can induce potentiation of this inhibitory connection that resembles the LTP induced by afferent tetanization. Furthermore, comparable acoustic stimulation produced a parallel decrease in the probability of the sound-evoked escape reflex. Thus we demonstrate for the first time, to our knowledge, a behavioural role for the long-term synaptic strengthening of inhibitory synapses.