We succeeded in isolating Chlamydia pneumoniae organisms continuously from a 70-year-old man who had received chemotherapeutic treatment with low dosages of erythromycin for five years to improve diffuse panbronchiolitis (DPB). He had two episodes of acute exacerbation of DPB and a total of six strains of C. pneumoniae were isolated at different stages during the past 13 months. The morphological properties and protein profiles of the elementary bodies of all the C. pneumoniae isolates were similar to each other. Interestingly, his serological response against C. pneumoniae in immunoblotting tests was differed between two episodes. The sera collected during the first episode reacted weakly to the major outer membrane protein (MOMP), whereas those collected during the second episode reacted strongly to the 60-kDa protein and weakly to MOMP. These facts suggest that the two different episodes occurred as a result of different mechanisms. Additionally, in spite of the low antibody titer by micro-immunofluorescence test in the second episode as compared with that of the first episode, the immune response against 60-kDa immunodominant protein increased markedly in the second episode, and we suspect that the second episode was due to an allergic reaction caused by this 60-kDa protein. These findings suggest that repeated or prolonged exposure to C. pneumoniae may be associated with acute exacerbations of chronic obstructive pulmonary disease, and that the patient should be noted as a possible source of C. pneumoniae infection.