Reduced pulmonary function is an important predictor of cardiovascular morbidity and mortality. The mechanisms underlying this association are unknown but may involve systemic inflammation. We assessed the cross-sectional and longitudinal relationships between C-reactive protein (CRP) levels and forced expiratory volume in 1 s (FEV 1) and its decline in the general population, over a period of 8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37±7 years, 50% women and 42% non-smokers), recruited at two French centers participating in the European Community Respiratory Health Survey. Lung function was expressed as a percentage of predicted FEV 1. CRP was measured centrally, by means of a highly sensitive assay. In cross-sectional analysis, FEV 1 as a % of predicted values was negatively associated with serum CRP concentration ( P = 0.002 ). Multivariate adjustment did not alter these results ( P = 0.002 ). In longitudinal analysis, annual FEV 1 decline tended to increase from the lower to the upper tertile for baseline CRP concentration but the association was borderline significant ( P = 0.14 ). Mean values of annual FEV 1 decline were 26±32, 31±32, and 34±32 ml/year for the lower, middle and upper tertiles of baseline CRP concentration, respectively, after adjusting for potential confounders ( P = 0.09 ). Changes in CRP levels during follow-up were associated with annual FEV 1 decline. The mean annual FEV 1 declines in subjects with increasing CRP, in those with stable CRP and in those with decreasing CRP were 36±31, 30±31 and 24±31 ml/year, respectively ( P < 0.001 ). These findings were not affected by adjustment for potential confounders ( P = 0.002 ). In conclusion, increases in CRP levels over time were associated with a steeper FEV 1 decline.