The first case was a 73-year-old woman with chief complaints of fever, cough, purulent sputum and dyspnea. EM therapy was begun in December 1983 due to a diagnosis of diffuse panbronchiolitis (DPB). Subsequently, P. aeruginosa was persistently detected, while in February 1991 at the time of an acute exacerbation of the DPB P. aeruginosa and S. pneumoniae were detected by TTA. The second case was a 65-year-old man with chief complaints of fever, cough and purulent sputum. DPB was diagnosed and EM therapy was begun in December 1985. In January 1991, pneumonia developed, at the time when S. pneumoniae was detected by TTA. In both cases, rapid disappearance of S. pneumoniae from the sputum and alleviation of symptoms were obtained with carbapenem antibiotic administration. Both strains were resistant to EM, Tetracycline (TC), Minocycline (MINO) and Clindamycin (CLDM). Particularly, S. pneumoniae of case 2 showed low sensitivity to Ampicillin (ABPC), Cefotiam (CTM) and Cefoxitin (CFX) as well. These cases showed acute exacerbations due to EM-resistant pneumococcus during long-term therapy with EM, and are of interest in that they may shed light on the relation between long-term EM therapy and the emergence of resistant pneumococcus.