C57BL/6 (C57) and DBA/2 (DBA) mice with dorsal hippocampus, central amygdala and sham lesions were observed for an eight-minute period, repeated on three consecutive days, in an open field situation with a novel object. Strain-dependent differences emerged when comparing sham lesioned mice; higher rearing and grooming scores as well as more defecation boli were found in DBA. In both strains, hippocampal lesions enhanced locomotor activity in the open field while amygdaloid lesions increased the number of contacts with the novel object. No significant lesion × strain interaction was recorded for any of the behaviours analyzed in the open field of the novelty situation. Significant strain × day, lesion × day and strain × lesion × day interactions were found thus indicating that previously described strain or lesion main effects were more pronounced on a particular day of testing. Despite the behavioural differences shown by sham lesioned C57 and DBA mice, the effects of the lesions differ in intensity but generally go in the same direction whatever the strain considered. Thus, while a strain-dependent selective involvement of subcortical areas in associative spatial learning has been previously reported, this does not seem to be the case for non-associative forms of learning.