Neuronal membrane channels ofDrosophila melanogasterwere altered either genetically or pharmacologically in order to investigate the role of specific ionic currents in the acquisition and retention of a conditioned behavior. Conditioning could not be detected forShakermutants, in which the fast transient potassium current (IA) is altered; a second potassium channel mutant,eag(ether a go-go) is conditioned like wild type, but the retention period is abnormally short. Thenaptsmutant (no action potential, temperature sensitive), in which nerve excitability is reduced, also expresses normal acquisition and a shortened period of retention. Double mutants ofSh5andnaptsas well asSh5treated with tetrodotoxin, are essentially normal with respect to acquisition; in both cases these flies remain retention-defective. These experiments therefore reveal a behavioral phenotype ofDrosophilamutants in which the primary physiological defect seems to be in the functioning of specific neuronal ionic channels.