Two separate acute bacterial exacerbations of chronic bronchitis and/or asthma were treated in 22 patients in a double-blind crossover study. One course of treatment consisted of 750 mg of ciprofloxacin twice daily and the other of 500 mg of ampicillin four times a day; each drug was given for 14 days. Patients were observed initially, every three to four days during therapy, and weekly during the post-therapy period. Observations that were recorded included graded chest symptoms and physical findings, vital signs, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, bacterial counts, and physical properties). Both antibiotic regimens were effective in resolving these acute bacterial exacerbations. Paired t test analysis revealed that ciprofloxacin is as clinically effective as ampicillin in the treatment of acute bacterial exacerbations in chronic bronchial disease, and appears to be superior in clearing bacterial pathogens from the sputum.