The tail-withdrawal reflex of Aplysia can be sensitized by weak stimulation of a site outside the site used to test the reflex or by repeatedly stimulating the test site itself. The sensitization of tail-withdrawal responses is associated with enhanced activation of the tail motor neurons and heterosynaptic facilitation of the monosynaptic connections between the tail sensory neurons and tail motor neurons. This synaptic facilitation can occur under conditions in which neither posttetanic potentiation nor generalized changes in postsynaptic input resistance contribute to the facilitation. In addition to producing monosynaptic excitatory postsynaptic potentials (EPSPs), action potentials in tail sensory neurons often recruit longer latency polysynaptic input to the tail motor neurons during sensitization. Strong, noxious tail shock similar in intensity to that used previously for sensitization and aversive classical conditioning of other responses in Aplysia produces more heterosynaptic facilitation than does weak sensitizing stimulation. Heterosynaptic facilitation builds up progressively with multiple trials and lasts for hours. Very strong shocks to the tail can change the response characteristics of tail sensory neurons so that a prolonged, regenerative burst of spikes is elicited by a brief intracellular depolarizing pulse. This bursting response produced by sensitizing stimulation has not been described previously in Aplysia sensory neurons and can greatly amplify the synaptic input to tail motor neurons from the sensory neurons. In addition, strong shocks to the tail increase the duration and magnitude of individual sensory neuron action potentials. Sensitizing tail stimulation usually produces long-lasting depolarization of the tail motor neurons and often long-lasting hyperpolarization of the tail sensory neurons. The tail motor and sensory neurons show both increases and decreases of input resistance following sensitizing stimulation. However, the small, occasional increases in input resistance of the motor neuron are insufficient to explain the heterosynaptic facilitation produced by sensitizing stimulation. Serotonin (5-HT) application can mimic many of the effects of sensitizing tail shock, including facilitation of both tail withdrawal and the monosynaptic connections between tail sensory and motor neurons, hyperpolarizing and depolarizing responses in the tail sensory neurons, and an increase in the duration and magnitude of the sensory neuron action potential. In the nearly isolated sensory neuron soma, 5-HT usually produces a slow, decreased conductance depolarizing response, suggesting that the 5-HT-induced hyperpolarizing response see