Genetic factors and early life adversity both play a major role in the etiology of mood and anxiety disorders. Previous studies have shown that postnatal maternal separation (MS) can produce lasting abnormalities in emotion-related behavior and neuroendocrine responses to stress in rodents. The present study sought to examine the effects of repeated MS in eight different inbred strains of mice (129S1/SvImJ, 129P3/J, A/J, BALB/cJ, BALB/cByJ C57BL/6J, DBA/2J, FVB/NJ). Pups were separated from their dam and littermates for 180min/day (‘MS’) or 15min/day (‘handling’), or left undisturbed (‘facility-reared’) from postnatal days P0-P13, and tested as adults for anxiety- and depression-related behaviors. Results demonstrated no clear and consistent effects of MS or handling on behavioral phenotypes in any of the strains tested. In all strains, MS produced an increase in maternal care on reunion with pups, which may have modified MS effects. Data demonstrate that the MS procedure employed does not provide a robust model of early life stress effects on the anxiety- and depression-related behaviors in the mouse strains tested.