Background: Low social support has been associated with several disorders. We test the relationship between perceived interpersonal social support (ISS) and aspects of mental and physical health. Methods: We used data from National Epidemiological Survey on Alcohol and Related Conditions in which 34 653 individuals aged 20-99 years were interviewed twice (2001-02 and 2004-05), with the second interview including the interpersonal support evaluation list. The association of perceived ISS with lifetime DSM-IV psychopathology and physical health from the past 12 months was investigated. We also tested whether this association changes as a function of number of traumatic events in accordance with the buffering hypothesis. Results: Low perceived ISS correlated with increased prevalence of major depressive disorder, generalized anxiety, social phobia and several physical health problems. There was a strong association between excellent self-perceived physical health and high social support. Conclusions: There was evidence for both the main, beneficial effects of high perceived ISS and buffering, whereby increased perceived ISS ameliorated the pathogenic influence of exposure to traumatic life events on psychopathology. Current findings highlight the importance of perceived ISS in individuals' general mental and physical well-being, both in daily life and upon exposure to negative life events.