Twenty-five patients with chronic bronchitis were studied intensively from 1968 to 1972. Viral, bacteriologic, mycologic, and mycoplasmal studies, both serologic and cultural, were carried out in an attempt to determine the role these agents play in exacerbations. All of the usual viral agents associated with exacerbations and 2 members of the coronavirus group, 229E and OC43, were detected. One third (33.6 per cent) of the 116 exacerbations observed could be related to viral infection or Mycoplasma pneumoniae (1 exacerbation). Viral infection was also noted to occur during periods of remission but was more commonly associated with periods of exacerbation(P less than 0.001). No interrelationship between viral and bacterial infection was apparent and neither Streptococcus pneumoniae nor Haemophilus influenzae was present more frequently in the sputum of patients in exacerbation. However, the number of S. pneumoniae organisms present in the sputum was significantly greater (P=0.04) during exacerbation than during remission and their presence was significatnly correlated with increases sputum purulence (P LESS THAN 0.01). This was not true of H. influenzae. Ampicillin was effective in clearing the sputum of S. pneumoniae but not of H. influenzae; the reverse was true of tetracycline.