An in vitro analogue of long-term behavioral training in Aplysia was developed to simulate the intensity and timing of shocks delivered to the body wall of animals during sensitization training. The in vitro training analogue consisted of electrical stimulation of peripheral nerves of isolated pleural-pedal ganglia. We found that the in vitro training analogue led to long-term (24 h) changes in the membrane currents of sensory neurons; these changes were similar to those produced by behavioral training. Using two dimensional polyacrylamide gel electrophoresis, we examined early effects on protein synthesis in pleural sensory neurons induced by the training analogue. Incorporation of amino acid into 5 proteins was affected at the end of training. Incorporation of amino acid into some of these proteins was also affected by serotonin (5-HT) and by an analogue of cyclic adenosine monophosphate (cAMP). These results suggest that the effects on protein synthesis that are produced by the in vitro training analogue are mediated, at least in part, by release of 5-HT and an increase in the level of cAMP in the sensory neurons.