The P3, or P300 component of the event-related potentials (ERPs) is a positive going waveform that can be averaged from the EEG approximately 250-500 ms following the presentation of task or context 'relevant' stimuli. This potential has been demonstrated to be a sensitive measure of both normal and abnormal cognitive functioning. P300 models have been developed in monkeys, cats and rats. The aim of the present study was to develop an auditory ERP paradigm suitable for use in mice that resembled those used in humans and other animal models. The results of the studies showed that late positive potentials in the 200-400 ms range could be generated in cortical sites in response to auditory stimuli. Additionally, like passive ERPs recorded in humans, mouse ERPs were sensitive to changes in stimulus characteristics. An earlier negative component designated the N1 was found to be sensitive to tone frequency and loudness but not to stimulus probability, whereas the mouse P300 component was sensitive to probability but not to tone frequency or loudness. C57BL/6 mice, a strain known to have a strong alcohol preference, were found to have significantly lower P300 amplitudes when compared to the DBA/2 strain. These findings also parallel human studies, and studies of selected lines of rats, demonstrating that decrements in P300 amplitude can be associated with a genetic vulnerability to alcoholism/alcohol preference. These studies further suggest that ERPs are an electrophysiological assay suitable for the exploration of the effects of genetic manipulations on neurosensory processing in mice.