Members of the ubiquitous 14-3-3 family of proteins are abundantly expressed in metazoan neurons. The Drosophila 14-3-3zeta gene leonardo is preferentially expressed in adult mushroom bodies, centers of insect learning and memory. Mutants exhibit defects in olfactory learning and memory and physiological neuroplasticity at the neuromuscular junction. Because strong mutations in this gene are lethal, we investigated the nature of the defects that precipitate the learning and memory deficit and the role of the two protein isoforms encoded by leonardo in these processes. We find that the behavioral deficit in the mutants is not caused by aberrant development, LEONARDO protein is acutely required for learning and memory, and both protein isoforms can function equivalently in embryonic development and behavioral neuroplasticity.