A training procedure analogous to differential classical conditioning produces differential facilitation of excitatory postsynaptic potentials (EPSP's) in the neuronal circuit for the siphon withdrawal reflex in Aplysia. Thus, tail shock (the unconditioned stimulus) produces greater facilitation of the monosynaptic EPSP from a siphon sensory neuron to a siphon motor neuron if the shock is preceded by spike activity in the sensory neuron than if the shock and spike activity occur in a specifically unpaired pattern or if the shock occurs alone. Further experiments indicate that this activity-dependent amplification of facilitation is presynaptic in origin and involves a differential increase in spike duration and thus in Ca2+ influx in paired versus unpaired sensory neurons. The results of these cellular experiments are quantitatively similar to the results of behavioral experiments with the same protocol and parameters, suggesting that activity-dependent amplification of presynaptic facilitation may make a significant contribution to classical conditioning of the withdrawal reflex.