The mechanosensory neuron that innervates the anteronotopleural bristle of Drosophila melanogaster responds with a burst of action potentials to deflection of the bristle towards the body wall. The decay of the firing rate upon sustained deflection is typical of a slowly adapting mechanosensory neuron. Upon repeated monotonous stimulation, the response decreases and the kinetics of adaptation change; the response recovers after rest. This sensory fatigue depends on the duration of the stimuli and the rate of stimulation. Two mutants, rutabaga (rut) and dunce (dnc), which are defective in learning and in the activity of the cAMP cascade, show altered kinetics of sensory fatigue. In rut, which has a reduced cAMP synthesis, the mechanosensory neuron fatigues less rapidly, whereas in dnc, characterized by a reduced cAMP hydrolysis, the neuron fatigues more rapidly than in wild-type flies. The data suggest that the cAMP cascade plays a role in the mechanism of sensory fatigue. Our study shows, for the first time, the effect of memory mutations on functional properties of an identified neuron which subserves a modifiable behavior. The experimental system described here could also be useful for neurogenetic dissection of mechanosensory transduction.