Long-term potentiation (LTP) of Aplysia sensorimotor synapses in cell culture can be induced by pairing sensory neuron activity with depolarization of the motorneuron. This pairing-induced LTP is prevented by perfusion with D,L-2-amino-5-phosphononovalerate (APV), a selective antagonist for the N-methyl-D-asparate (NMDA) subclass of glutamate receptors. Repeated pairing of presynaptic activity with postsynaptic depolarization induces LTP comprising both APV-sensitive and APV-insensitive components. Infusing BAPTA, a selective Ca2+ chelator, into the postsynaptic motoneuron completely blocks pairing-induced LTP. These results demonstrate that Aplysia sensorimotor synapses are capable of hebbian LTP-similar to that exhibited by synapses in the mammalian hippocampus - and suggest a role for this type of synaptic plasticity in classical conditioning of the defensive withdrawal reflex of Aplysia.