Latent inhibition (LI) consists of decreased associative strength between an elemental stimulus (CS: tone) paired with an unconditioned stimulus (US: footshock) following non-reinforced pre-exposure to the tone. In view of the differences shown by C57BL/6 (C57) and DBA/2 (DBA) mice in processing elemental vs. configural stimuli, the present experiments were designed (1) to assess whether these differences were likely to interfere with the capability of each strain to show LI, and (2) to verify the extent to which lesions of the nucleus accumbens, which have been reported to enhance attention towards contextual stimuli under certain conditions, might interfere with the development of LI. C57 and DBA mice with Nacc or sham lesions were given two periods (4 or 7 days) of pre-exposure to a CS (tone) then subjected to two CS-US pairings given on a single day. On the day after, freezing to the tone was examined in each group. Results show that, following the shorter period of pre-exposure, LI developed in sham-lesioned DBA but did not in sham-lesioned C57. Nacc lesions, however, were found (1) to block LI in DBA but (2) to promote LI in C57. After the longer period of pre-exposure LI was observed in both strain and lesion conditions. In general, these results confirm that strain differences in processing the tone as a single elemental cue (DBA) or, alternatively, as a part of a contextual configural stimulus (C57) can interfere with the development of LI. In addition, they indicate that Nacc lesions, that are susceptible to increase attention to the background, might modify the salience of the tone and produce opposite effect on LI according to the strain specialisation to show elemental or configural responding.