Several studies have stressed a correlation between difficulties in acculturation and mental distress or even mental disorders. The stress related to the process of acculturation can lead to depressive symptoms by way of changes in the activity of the HPA axis. However, it remains difficult to measure acculturation stress, as difficulties in acculturation strongly depend on subjective interpretations of every day experiences. The association between acculturation stress and mental distress was examined in two different migrant groups in Germany, 202 migrants of Russian and 100 of Iranian origin. In both migrant groups a significant correlation between acculturation stress and mental distress was found, yet no significant association between acculturation stress and length of residency in Germany. These findings will have to be replicated with representative samples and also with other migrant groups, both in and out of treatment. Considering the fact that the Russian sample was younger and nonetheless had relatively high acculturation stress scores, prevention of future mental health problems among migrants will have to focus on easing the process of integration into the host society.