The gill- and siphon-withdrawal reflex of Aplysia undergoes classical conditioning of its amplitude and duration when siphon stimulation (the conditioned stimulus, CS) is paired with tail or mantle shock (the unconditioned stimulus, US). This conditioning of a preexisting response exhibits both temporal and stimulus specificities, which can be accounted for by activity-dependent enhancement of presynaptic facilitation of the siphon sensory neurons. To test whether conditioning of the reflex also exhibits response specificity (development of a new type of response to the CS that often resembles the response to the US), we measured the direction of siphon withdrawal in response to siphon stimulation (the CS) with tail or mantle shock as the US. The unlearned response to siphon stimulation is straight contraction, the response to tail shock is backward bending, and the response to mantle shock is forward bending. In the first experiment, we trained different animals with the tail or mantle US paired or unpaired with the CS; in a second experiment, we trained each animal with two CSs, one of which was paired with the US; in a third experiment, we varied US intensity; and in a fourth experiment, we trained each animal with two USs, one of which was paired with the CS. There was a significant, pairing-specific tendency for the direction of the response to the CS to resemble the response to the US after training in each experiment, demonstrating response specificity in conditioning of the withdrawal reflex. This feature of conditioning could in principle be accounted for by an elaboration of activity-dependent facilitation.