BACKGROUND: In the field of respiratory tract infections (RTI), concern about the efficiency of various treatments has increased with the introduction of newer antibiotics often associated with higher acquisition costs. These include second-generation macrolides and fluoroquinolones, which constitute alternative strategies to amoxicillin and erythromycin. OBJECTIVES: To evaluate, from a cost-efficacy standpoint, how these newer agents compare with each other in the treatment of community acquired RTI in adults. METHODS: Cost-efficacy analyses were done using decision-analysis techniques based on efficacy and safety data of published clinical trials. The analyses were performed from the perspective of a provincial third-party payer. Costs considered were those of antibiotics, physicians and pharmacists services and diagnostic procedures. RTI for which analyses were performed are: bronchitis, community acquired pneumonia, otitis media, pharyngitis and sinusitis. Specific antibiotics compared were: azithromycin, ciprofloxacin, clarithromycin, grepafloxacin, levofloxacin and ofloxacin. RESULTS: Following a review of the literature using Medline and Current Contents, 98 articles published between January 1986 and December 1999 met the inclusion criteria and provided efficacy and safety data for the analyses. Efficacy rates for each antibiotic did not differ strikingly and various dosages did not necessarily have an impact on efficacy rates. Cost-efficacy analyses indicate that, among the antibiotics studied, the lowest cost-efficacy ratios were associated with either azithromycin or clarithromycin at a dose of 250mg twice daily. Azithromycin represented the preferred strategy for the ambulatory treatment of community-acquired pneumonia and otitis media, while clarithromycin at a dose of 250 mg twice daily would be preferable for bronchitis, pharyngitis and sinusitis. The studied fluoroquinolones and clarithromycin at a dose of 500 mg twice daily were dominated strategies for each of the studied RTI. CONCLUSION: From a cost-efficacy standpoint clarithromycin and azithromycin would be preferable to fluoroquinolones when an alternate strategy to amoxicillin or erythromycin is needed.