Long-term sensitization training induces persistent changes in both electrophysiological properties and specific structural features of sensory neurons in Aplysia californica. Previously, we found that transient elevation of intracellular cAMP could also modify these features in sensory neurons located in the pleural ganglion. In the present study we examined the role of protein synthesis in structural remodeling induced by cAMP. When applied during the intracellular injection of cAMP, anisomycin blocked increases in both the number of varicosities and the number of branch points in single sensory neurons. Exposure to anisomycin during different time periods, from as early as 12 hr prior to cAMP injection to periods as late as 15 hr after, indicated that the requirement for protein synthesis starts at the time of cAMP injection and extends for at least seven hours afterwards. Because it is metabolized rapidly, cAMP probably triggers a cascade of protein synthesis whose products continue to be synthesized for several hours after cAMP levels have returned to baseline. Thus, the present results suggest that the induction of long-term structural changes in sensory neurons has an extended but finite requirement for protein synthesis.