The seroprevalence of Chlamydia pneumoniae is increased in chronic obstructive pulmonary disease (COPD), and subjects with COPD are more likely to have a positive polymerase chain reaction for C. pneumoniae in their sputum. It has been suggested that C. pneumoniae may have a role in the pathogenesis of COPD. We undertook immunohistochemistical staining for C. pneumoniae in archival tissue from subjects who had undergone lobectomy for bronchial carcinoma. There were 16 subjects with COPD (FEV(1) = 64 +/- 8% [mean +/- SD] predicted) and 21 subjects with normal lung function (FEV(1) = 95 +/- 11% predicted). There was no difference between the two groups in age or smoking history. Tissues from all of the subjects stained positively for C. pneumoniae, but in the subjects with COPD there were 14.5 positive cells per field (magnification x400), as compared with 9.3 cells per field in the control subjects (p = 0.02). Fifty-four percent of the macrophages from the subjects with COPD stained positively for C. pneumoniae, as compared with 29% from the control subjects (p < 0.001). A second control group consisted of 18 younger individuals (mean age: 32 yr) who died accidentally. Only 44% of these subjects had positive staining for C. pneumoniae, and the mean number of cells per field was 0.4. These findings suggest that persistent infection with C. pneumoniae is common, and that there is increased immunostaining for C. pneumoniae in COPD. Further studies are necessary to determine whether chronic infection with C. pneumoniae is important in the pathogenesis of COPD.