To assess whether two inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and change in their concentrations over 12 years, are associated with lung function (FVC and FEV(1)) 12 years after baseline. Data are from over 1,500 participants free from self-reported respiratory problems in a large-scale prospective cohort study of white-collar male and female civil servants. CRP and IL-6 measured at baseline (1991-1993) and follow-up (2002-2004) and FVC and FEV(1), measured at follow-up. Results adjusted for sociodemographic and anthropometric characteristics, health behaviours, biological factors, chronic conditions and medications, and corrected for short-term variability in CRP and IL-6 concentrations. Higher baseline levels of CRP and IL-6 were strongly associated with lower FVC and FEV(1), independent of potential confounders. A 10% increase serum CRP from baseline to follow-up was associated with lower values of FVC and FEV(1) at follow-up, 4.7 and 3.0 ml, respectively. The corresponding values for a 10% increase in IL-6 were 12.6 ml for FVC and 7.3 ml for FEV(1). Systemic low-grade inflammation is associated with only slightly poorer pulmonary function in a population free from self-reported respiratory problems 12 years earlier. These data provide evidence linking inflammation to adverse outcomes beyond cardiovascular disease. Interventions targeting inflammation may prevent lung function impairment.