The inflammation hypothesis of depression, or more broadly, common mental disorders, proposes that chronic inflammation plays an important role in the pathophysiology of these conditions. 1, 2 The hypothesis is supported by experiments of inflammatory stimuli, antidepressant trials and studies on depression-related genes and pathogen host defense, 2–5 but direct population-based evidence from long-term inflammation is scarce. Because of a lack of studies on the effects of chronically elevated inflammation, assessed over several years using repeat measurements, it has remained unclear whether the association between inflammation and common mental disorder is the consequence of acute or chronic inflammation. This report is from the Whitehall II cohort study. 6 In our analysis of up to 4630 adults without chronic disease, we used repeat measures of inflammatory markers and mental disorder. We measured the proinflammatory cytokine interleukin 6 (IL-6) in 1992, 1997 and 2003 and common mental disorder, based on the General Health Questionnaire (GHQ), in 1997, 2003 and 2008. The IL-6 distribution was categorized as: p1. 0 pg mlÀ 1 (low), 1.1–2.0 pg mlÀ 1 (intermediate) and 42.0 pg mlÀ 1 (high). Details