The effects of familiarity on auditory change detection on the basis of auditory sensory memory representations were investigated by presenting oddball sequences of sounds while participants ignored the auditory stimuli. Stimulus sequences were composed of sounds that were familiar and sounds that were made unfamiliar by playing the same sounds backward. The roles of frequently presented stimuli (standards) and infrequently presented ones (deviants) were fully crossed. Deviants elicited the mismatch negativity component of the event-related brain potential. We found an enhancement in detecting changes when deviant sounds appeared among familiar standard sounds compared when they were delivered among unfamiliar standards. Familiarity with the deviant sounds also enhanced the change-detection process. We suggest that tuning to familiar items sets up preparatory processes that affect change detection in familiar sound sequences.