Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.