This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.