Long-term potentiation (LTP) has been proposed as a cellular mechanism for associative learning in vertebrates. Induction of one type of LTP--observed at synapses in the CA1 region of the mammalian hippocampus--is regulated by the voltage of the postsynaptic cell. To date, a similar form of LTP has not been demonstrated for any invertebrate synapse. We now report that high-frequency stimulation can induce LTP of sensorimotor synapses of the marine mollusc Aplysia in cell culture. Moreover, induction of this form of LTP appears to involve a voltage-dependent postsynaptic mechanism because pairing tetanic stimulation of the presynaptic cell with strong hyperpolarization of the postsynaptic cell blocks the induction of LTP.