Allostatic load theory implies a relationship between exposure to psychological stress and multi-system physiological dysregulation. We used data from population-based samples of men and women in Russia (Moscow; n ¼ 1800; age, mean 68.6 years), Taiwan (n ¼ 1036; 65.6 years) and the United States (US; n ¼ 1054; 58.0 years) – which are likely to vary widely with respect to levels of stress exposure and biological markers – to determine the magnitude of the association between perceived stress and physiological dysregulation. The measure of overall dysregulation was based on 15 markers including standard cardiovascular/metabolic risk factors as well as markers of inflammation and neuroendocrine activity. Subjective psychological stress was measured by the perceived stress scale. Only the Moscow sample demonstrated a positive association with overall dysregulation in both sexes. In the US, we found an association among women but not men. Among the Taiwanese, who report the lowest perceived stress, there was no association in women but an unexpected inverse relationship in men. The effects also varied across system-level subscores: the association with perceived stress was most consistent for standard cardiovascular/metabolic factors. Perceived stress was associated with inflammation and neuroendocrine activity in some samples. Although the evidence that perceived stress is the primary source of physiological dysregulation is generally modest, it was stronger in Russia where the level of perceived stress was particularly high. For Russia only, we had information about heart function based on a 24 h ambulatory electrocardiogram; perceived stress was consistently associated with heart rate dysregulation in Russian men and women.