On repetitive stimulation, the strength of a reflex controlling leg position inDrosophiladecreased, and this response decrement conformed to the parametric features of habituation. To study the presynaptic function of CaMKII in this nonassociative form of learning, we used a P[Gal4] insertion line to target the expression of mutant forms of CaMKII to the sensory neurons controlling the reflex. Targeted expression of a calcium-independent CaMKII construct (T287D) in the sensory neurons eliminated habituation. Targeted expression of a mutant CaMKII incapable of achieving calcium independence (T287A) reduced the initial reflex response, but a strong facilitation then occurred, and this eliminated most of the habituation. Finally, when a CaMKII inhibitory peptide (ala) was expressed in sensory neurons, the initial response was reduced, followed by facilitation. These results suggest that basal CaMKII levels in the presynaptic neurons set the response level and dynamics of the entire neural circuit.